Scholars@Duke
David A D'Alessio

David A D'Alessio

Lindquist Presidential Distinguished Chair
Medicine, Endocrinology, Metabolism, and Nutrition
david.d'alessio@duke.edu
DUMC Box 104775, Durham, NC 27710
300 North Duke Street, Durham, NC 27701

Selected Publications

Impact of glucagon-like peptide-1 receptor agonists on diabetic retinopathy: A meta-analysis of clinical studies emphasising retinal changes as a primary outcome.

Journal Article Clin Exp Ophthalmol · September 26, 2024 BACKGROUND: To determine if glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with the development and progression of diabetic retinopathy (DR). METHODS: A systematic search was conducted on PubMed, Cochrane Library, and Embase from incept ... Full text Link to item Cite

A look at duodenal mucosal resurfacing: Rationale for targeting the duodenum in type 2 diabetes.

Journal Article Diabetes Obes Metab · June 2024 Affecting 5%-10% of the world population, type 2 diabetes (T2DM) is firmly established as one of the major health burdens of modern society. People with T2DM require long-term therapies to reduce blood glucose, an approach that can mitigate the vascular co ... Full text Link to item Cite

High Doses of Exogenous Glucagon Stimulate Insulin Secretion and Reduce Insulin Clearance in Healthy Humans.

Journal Article Diabetes · March 1, 2024 Glucagon is generally defined as a counterregulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP) in response to hypoglycemia. However, glucagon has long been known to stimulate insulin ... Full text Link to item Cite

Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics.

Journal Article Am Heart J · January 2024 BACKGROUND: Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outc ... Full text Link to item Cite

Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2023 The incretin effect describes the insulin response to nutrient ingestion that exceeds the response to glycemia per se. It is mediated by gastrointestinal factors and is necessary to maintain postprandial glucose homeostasis. The incretin effect results in ... Full text Link to item Cite

GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications.

Journal Article Cell Metab · September 5, 2023 The incretin system is an essential metabolic axis that regulates postprandial metabolism. The two incretin peptides that enable this effect are the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide 1 (GLP-1), which have cogn ... Full text Link to item Cite

Classics in Diabetes.

Journal Article Diabetes · September 1, 2023 Full text Link to item Cite

The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets.

Journal Article Nat Metab · June 2023 The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake to facilitate glucose tolerance1. The GLP-1 receptor (GLP-1R) is an established drug ta ... Full text Link to item Cite

The ubiquitination status of the glucagon receptor determines signal bias.

Journal Article J Biol Chem · May 2023 The pancreatic hormone glucagon activates the glucagon receptor (GCGR), a class B seven-transmembrane G protein-coupled receptor that couples to the stimulatory heterotrimeric G protein and provokes PKA-dependent signaling cascades vital to hepatic glucose ... Full text Link to item Cite

Risk factors for the development or progression of diabetic retinopathy in pregnancy: Meta-analysis and systematic review.

Journal Article Clin Exp Ophthalmol · April 2023 BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population, and it increases in severity during pregnancy. METHODS: Systematic review of literature from PubMed, Cochrane Library and Web of Science using keywords ' ... Full text Link to item Cite

An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.

Journal Article Biomaterials · March 2023 Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. However, the improvement in the plasma half-life of PEGylated drugs' is at an asymptote because the development of bran ... Full text Link to item Cite

GLP-1 receptor agonists and diabetic retinopathy: A meta-analysis of randomized clinical trials.

Journal Article Surv Ophthalmol · 2023 Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes mellitus. Recent research suggests that GLP-1 RAs may influence diabetic retinopathy (DR). We searched ClinicalTrials.gov for trials comparing FDA-approved GLP-1 RAs to ... Full text Link to item Cite

The Impact of Pregnancy on Diabetic Retinopathy: A Single-Site Study of Clinical Risk Factors.

Journal Article Ophthalmic Res · 2023 INTRODUCTION: This study aimed to provide information on modifiable and non-modifiable risk factors for the progression and development of diabetic retinopathy (DR) and diabetic macular edema (DME). This retrospective chart review case-control study was de ... Full text Link to item Cite

Discovery of a potent GIPR peptide antagonist that is effective in rodent and human systems.

Journal Article Mol Metab · December 2022 OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is one of the two major incretin factors that regulate metabolic homeostasis. Genetic ablation of its receptor (GIPR) in mice confers protection against diet-induced obesity (DIO), while GIPR ne ... Full text Link to item Cite

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.

Journal Article Lancet · November 26, 2022 BACKGROUND: Treating hyperglycaemia and obesity in individuals with type 2 diabetes using multi-receptor agonists can improve short-term and long-term outcomes. LY3437943 is a single peptide with agonist activity for glucagon, glucose-dependent insulinotro ... Full text Link to item Cite

The past, present, and future physiology and pharmacology of glucagon.

Journal Article Cell metabolism · November 2022 The evolution of glucagon has seen the transition from an impurity in the preparation of insulin to the development of glucagon receptor agonists for use in type 1 diabetes. In type 2 diabetes, glucagon receptor antagonists have been explored to reduce gly ... Full text Cite

Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis.

Journal Article Diabetes · October 1, 2022 Impaired insulin and incretin secretion underlie abnormal glucose tolerance (AGT) in pancreatic insufficient cystic fibrosis (PI-CF). Whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can e ... Full text Link to item Cite

GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1.

Journal Article J Clin Endocrinol Metab · August 18, 2022 CONTEXT: Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have be ... Full text Link to item Cite

Slow and Steady Wins the Race: 25 Years Developing the GLP-1 Receptor as an Effective Target for Weight Loss.

Journal Article J Clin Endocrinol Metab · July 14, 2022 Recent evidence from clinical trials supports the efficacy and tolerability of glucagon-like peptide 1 (GLP-1) receptor agonists as useful agents for weight loss. Although originally developed as glucose lowering agents for people with type 2 diabetes, pro ... Full text Link to item Cite

Evaluation of a deep learning supported remote diagnosis model for identification of diabetic retinopathy using wide-field Optomap

Journal Article Annals of Eye Science · June 1, 2022 Background: We test a deep learning (DL) supported remote diagnosis approach to detect diabetic retinopathy (DR) and other referable retinal pathologies using ultra-wide-field (UWF) Optomap. Methods: Prospective, non-randomized study involving diabetic pat ... Full text Cite

GIPR Is Predominantly Localized to Nonadipocyte Cell Types Within White Adipose Tissue.

Journal Article Diabetes · May 2022 The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) augments glucose-dependent insulin secretion through its receptor expressed on islet β-cells. GIP also acts on adipose tissue; yet paradoxically, both enhanced and reduced GIP receptor ... Full text Cite

Utility of Continuous Glucose Monitoring vs Meal Study in Detecting Hypoglycemia After Gastric Bypass.

Journal Article J Clin Endocrinol Metab · April 19, 2022 CONTEXT: Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose and relief of sym ... Full text Link to item Cite

Data from: GLP-1 receptor blockade reduces stimulated insulin secretion in fasted subjects with low circulating GLP-1

Dataset · January 26, 2022 Context: Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have lo ... Full text Cite

198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects

Conference Diabetes · June 1, 2021 Glucagon is generally considered to be a counter-regulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP). However, recent preclinical findings support a paracrine action of gluc ... Full text Cite

781-P: Beyond Glucosuria: Urine Metabolome Signature Associated with Dapagliflozin in Wild-Type Mice

Conference Diabetes · June 1, 2021 Background: Glucosuria is a hallmark feature of diabetes. When blood glucose exceeds 200 mg/dl, the amounts reaching the renal tubule overwhelm the capacity of glucose transport and cause glucosuria. SGLT2 inhibitors (SGLT2i) prevent reclamation of ... Full text Cite

GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells.

Journal Article Sci Adv · March 2021 Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon ... Full text Link to item Cite

Brain control of blood glucose levels: implications for the pathogenesis of type 2 diabetes.

Journal Article Diabetologia · January 2021 Despite a rapidly growing literature, the role played by the brain in both normal glucose homeostasis and in type 2 diabetes pathogenesis remains poorly understood. In this review, we introduce a framework for understanding the brain's essential role in th ... Full text Link to item Cite

Correction to: Brain control of blood glucose levels: implications for the pathogenesis of type 2 diabetes.

Journal Article Diabetologia · January 2021 The authors wish to point out a typographical error. ... Full text Link to item Cite

Injectable non-immunogenic PEG-like conjugate that forms a subcutaneous depot and enables sustained delivery of a peptide drug

Journal Article · 2021 Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. Unfortunately, PEG is immunogenic and forms vacuoles, and improvement in PEGylated drugs' half-life is at an asymptote. ... Full text Cite

Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.

Journal Article JCI Insight · September 3, 2020 Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic steatohepatitis. Early phase trials in T2DM indicate that tirzepatide improves clinical outco ... Full text Link to item Cite

Discordance between GLP-1R gene and protein expression in mouse pancreatic islet cells.

Journal Article J Biol Chem · August 14, 2020 The insulinotropic actions of glucagon-like peptide 1 receptor (GLP-1R) in β-cells have made it a useful target to manage type 2 diabetes. Metabolic stress reduces β-cell sensitivity to GLP-1, yet the underlying mechanisms are unknown. We hypothesized that ... Full text Link to item Cite

Sustained release of a GLP-1 and FGF21 dual agonist from an injectable depot protects mice from obesity and hyperglycemia.

Journal Article Sci Adv · August 2020 There is great interest in identifying a glucagon-like peptide-1 (GLP-1)-based combination therapy that will more effectively promote weight loss in patients with type 2 diabetes. Fibroblast growth factor 21 (FGF21) is a compelling yet previously unexplore ... Full text Link to item Cite

The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition.

Journal Article Diabetes · May 2020 Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote ketosis in the fas ... Full text Link to item Cite

Thermic effect of food and resting energy expenditure after sleeve gastrectomy for weight loss in adolescent females.

Journal Article Surg Obes Relat Dis · May 2020 BACKGROUND: Few studies have addressed the effect of bariatric surgery on factors related to energy balance, including resting energy expenditure (REE) and thermic effect of food (TEF). To our knowledge, very few studies have examined changes in REE and no ... Full text Link to item Cite

THE EFFECTS OF PERIOPERATIVE DEXAMETHASONE ON GLYCEMIC CONTROL AND POSTOPERATIVE OUTCOMES.

Journal Article Endocr Pract · February 2020 Objective: Perioperative glucocorticoids are commonly given to reduce pain and nausea in patients undergoing surgery. However, the glycemic effects of steroids and the potential effects on morbidity and mortality have not been systematically evaluated. Thi ... Full text Link to item Cite

Rapid hepatic metabolism blunts the endocrine action of portally infused GLP-1 in male rats.

Journal Article Am J Physiol Endocrinol Metab · February 1, 2020 Glucagon-like peptide-1 (GLP-1) is an enteral peptide that contributes to the incretin effect. GLP-1 action is typically described as endocrine, but this mechanism has been questioned because rapid inactivation in the circulation by dipeptidylpeptidase 4 ( ... Full text Link to item Cite

2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

Journal Article Diabetologia · February 2020 The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycaemia, based on important research findings from large cardiovascular outcomes trials publish ... Full text Link to item Cite

2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

Journal Article Diabetes Care · February 2020 The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials publishe ... Full text Link to item Cite

Pharmacological antagonism of the incretin system protects against diet-induced obesity.

Journal Article Mol Metab · February 2020 OBJECTIVE: Glucose-dependent insulinotropic polypeptide is an intestinally derived hormone that is essential for normal metabolic regulation. Loss of the GIP receptor (GIPR) through genetic elimination or pharmacological antagonism reduces body weight and ... Full text Link to item Cite

Efficacy and Safety of the Glucagon Receptor Antagonist RVT-1502 in Type 2 Diabetes Uncontrolled on Metformin Monotherapy: A 12-Week Dose-Ranging Study.

Journal Article Diabetes Care · January 2020 OBJECTIVE: Evaluate the safety and efficacy of RVT-1502, a novel oral glucagon receptor antagonist, in subjects with type 2 diabetes inadequately controlled on metformin. RESEARCH DESIGN AND METHODS: In a phase 2, double-blind, randomized, placebo-controll ... Full text Link to item Cite

Glucagon-like peptide 1 (GLP-1).

Journal Article Mol Metab · December 2019 BACKGROUND: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibiti ... Full text Link to item Cite

Effect of vitamin D supplementation on cardiovascular risk in type 2 diabetes.

Journal Article Clin Nutr · October 2019 BACKGROUND & AIMS: Whether vitamin D affects lipid profile and cardiovascular disease (CVD) risk is controversial. We evaluated the effect of oral daily vitamin D supplementation on lipid profile and CVD risk in patients with well-controlled type 2 diabete ... Full text Link to item Cite

Beta-cell sensitivity to insulinotropic gut hormones is reduced after gastric bypass surgery.

Journal Article Gut · October 2019 OBJECTIVE: Postprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory f ... Full text Link to item Cite

The Effects of Bariatric Surgery on Islet Function, Insulin Secretion, and Glucose Control.

Journal Article Endocr Rev · October 1, 2019 Although bariatric surgery was developed primarily to treat morbid obesity, evidence from the earliest clinical observations to the most recent clinical trials consistently demonstrates that these procedures have substantial effects on glucose metabolism. ... Full text Link to item Cite

Temporal plasticity of insulin and incretin secretion and insulin sensitivity following sleeve gastrectomy contribute to sustained improvements in glucose control.

Journal Article Mol Metab · October 2019 OBJECTIVE: Bariatric surgery acutely improves glucose control, an effect that is generally sustained for years in most patients. The acute postoperative glycemic reduction is at least partially mediated by enhanced incretin secretion and islet function, an ... Full text Link to item Cite

One small step for mice, one giant leap for GWAS?

Journal Article J Clin Invest · October 1, 2019 Genome-wide association studies (GWAS) have provided a wealth of information on potential disease-associated genes in the human population. In particular, several loci have been associated with type 2 diabetes (T2D). However, due to the complexity of the d ... Full text Link to item Cite

Intraislet Ghrelin Signaling Does Not Regulate Insulin Secretion From Adult Mice.

Journal Article Diabetes · September 2019 Exogenous ghrelin reduces glucose-stimulated insulin secretion and endogenous ghrelin protects against hypoglycemia during starvation. Islet ε-cells produce ghrelin and δ-cells express growth hormone secretagogue receptor (GHSR), suggesting the possibility ... Full text Link to item Cite

Glucagon lowers glycemia when β-cells are active.

Journal Article JCI Insight · July 23, 2019 Glucagon and insulin are commonly believed to have counteracting effects on blood glucose levels. However, recent studies have demonstrated that glucagon has a physiologic role to activate β-cells and enhance insulin secretion. To date, the actions of gluc ... Full text Link to item Cite

Role of vagal activation in postprandial glucose metabolism after gastric bypass in individuals with and without hypoglycaemia.

Journal Article Diabetes Obes Metab · June 2019 Patients who have undergone gastric bypass surgery (GB) have enhanced postprandial hyperinsulinaemia and a greater incretin effect is apparent. In the present study, we sought to determine the effect of vagal activation, a neural component of the enteroins ... Full text Link to item Cite

1016-P: A Novel GLP-1 and FGF-21 Dual Agonist Drug Protects Mice from Obesity and Hyperglycemia

Conference Diabetes · June 1, 2019 As the incidence of diabetes increases, the development of new therapeutic strategies is essential. Recent evidence supports combination therapies that incorporate complementary mechanisms of action as potent and effective. We have developed a unim ... Full text Cite

Sleeve gastrectomy rapidly enhances islet function independently of body weight.

Journal Article JCI Insight · March 21, 2019 Bariatric surgeries including vertical sleeve gastrectomy (VSG) ameliorate obesity and diabetes. Weight loss and accompanying increases to insulin sensitivity contribute to improved glycemia after surgery; however, studies in humans also suggest weight-ind ... Full text Link to item Cite

β Cell tone is defined by proglucagon peptides through cAMP signaling.

Journal Article JCI Insight · March 7, 2019 Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for α to β cell communication and con ... Full text Link to item Cite

Novel cancer therapies and their association with diabetes.

Journal Article J Mol Endocrinol · February 1, 2019 Over the last decade, there has been a shift in the focus of cancer therapy from conventional cytotoxic drugs to therapies more specifically directed to cancer cells. These novel therapies include immunotherapy, targeted therapy and precision medicine, eac ... Full text Link to item Cite

Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

Journal Article Diabetologia · December 2018 The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the li ... Full text Link to item Cite

Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

Journal Article Diabetes Care · December 2018 The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the li ... Full text Link to item Cite

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.

Journal Article Mol Metab · December 2018 OBJECTIVE: A novel dual GIP and GLP-1 receptor agonist, LY3298176, was developed to determine whether the metabolic action of GIP adds to the established clinical benefits of selective GLP-1 receptor agonists in type 2 diabetes mellitus (T2DM). METHODS: LY ... Full text Link to item Cite

Deletion of the glucagon receptor gene before and after experimental diabetes reveals differential protection from hyperglycemia.

Journal Article Mol Metab · November 2018 OBJECTIVE: Mice with congenital loss of the glucagon receptor gene (Gcgr-/- mice) remain normoglycemic in insulinopenic conditions, suggesting that unopposed glucagon action is the driving force for hyperglycemia in Type-1 Diabetes Mellitus (T1DM). However ... Full text Link to item Cite

Interaction of GLP-1 and Ghrelin on Glucose Tolerance in Healthy Humans.

Journal Article Diabetes · October 2018 Emerging evidence supports the importance of ghrelin to defend against starvation-induced hypoglycemia. This effect may be mediated by inhibition of glucose-stimulated insulin secretion as well as reduced insulin sensitivity. However, administration of ghr ... Full text Link to item Cite

Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a β-Cell Glucagon-Like Peptide 1 Receptor.

Journal Article Diabetes · August 2018 Bariatric surgeries, including vertical sleeve gastrectomy (VSG), resolve diabetes in 40-50% of patients. Studies examining the molecular mechanisms underlying this effect have centered on the role of the insulinotropic glucagon-like peptide 1 (GLP-1), in ... Full text Link to item Cite

Primary Adrenal Insufficiency from Immune Checkpoint Inhibitors

Journal Article AACE Clinical Case Reports · May 1, 2018 Objective: To describe a rare case of primary adrenal insufficiency (PAI) from immune checkpoint inhibitors (ICPIs). Methods: We describe the clinical presentation, supportive laboratory findings, long-term outcomes, and a review of the current available l ... Full text Cite

Beta-cell sensitivity to glucose is impaired after gastric bypass surgery.

Journal Article Diabetes Obes Metab · April 2018 AIMS: Patients who have undergone Roux-en-Y gastric bypass surgery (GB) have exaggerated postprandial insulin secretion, which has been attributed to increased meal glucose appearance and enhanced incretin effect. Here, we sought to determine β-cell glucos ... Full text Open Access Link to item Cite

Gastrointestinal hormones and the control of food intake and energy metabolism

Chapter · January 1, 2018 Gastrointestinal (GI) hormones are increasingly recognized for their roles in the control of appetite and obesity. In this chapter, we review selected regulatory factors secreted from the gut including ghrelin, glucagon-like peptide 1 (GLP-1), cholecystoki ... Full text Cite

Vitamin D supplementation in patients with type 2 diabetes: The vitamin D for established type 2 diabetes (DDM2) study

Journal Article Journal of the Endocrine Society · January 1, 2018 Context: Observational data support a role for vitamin D in type 2 diabetes, but evidence from trials is inconclusive. Objective: To evaluate the effect of vitamin D supplementation on β-cell function and hemoglobin A1c (HbA1c) in patients with well-contro ... Full text Cite

β-Cell Function Over Time in Adolescents With New Type 2 Diabetes and Obese Adolescents Without Diabetes.

Journal Article J Adolesc Health · December 2017 PURPOSE: The progression of β-cell function in newly diagnosed adolescents with type 2 diabetes mellitus (T2DM) is not well documented. We hypothesized that at the time of diagnosis with T2DM, adolescents would have impaired β-cell function as demonstrated ... Full text Link to item Cite

Metformin Use May Moderate the Effect of DPP-4 Inhibitors on Cardiovascular Outcomes.

Journal Article Diabetes Care · December 2017 OBJECTIVE: To explore prevalent metformin use as a potential moderator of the cardiovascular effects of dipeptidyl peptidase 4 inhibitors (DPP-4i). RESEARCH DESIGN AND METHODS: We performed a meta-analysis of the three major cardiovascular outcomes trials ... Full text Link to item Cite

Central Nervous System GLP-1 Receptors Regulate Islet Hormone Secretion and Glucose Homeostasis in Male Rats.

Journal Article Endocrinology · July 1, 2017 The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, princi ... Full text Link to item Cite

The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice.

Journal Article Cell Metab · April 4, 2017 Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To test the relative importance of intestinal versus pancreati ... Full text Link to item Cite

DREADDing proglucagon neurons: a fresh look at metabolic regulation by the brain.

Journal Article J Clin Invest · March 1, 2017 Glucagon-like peptide 1 receptor (GLP-1R) signaling in the CNS has been linked to reduced food intake, lower body weight, improved glucose homeostasis, and activation of CNS stress axes. GLP-1 is produced by cells that express proglucagon (GCG); however, t ... Full text Link to item Cite

Acute administration of acyl, but not desacyl ghrelin, decreases blood pressure in healthy humans.

Journal Article Eur J Endocrinol · February 2017 OBJECTIVE: To compare the effects of acyl ghrelin (AG) and desacyl ghrelin (DAG) on blood pressure (BP), heart rate (HR) and other autonomic parameters in healthy humans and to elucidate the hormonal mechanisms through which AG could exert its cardiovascul ... Full text Link to item Cite

Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress.

Journal Article J Neurosci · January 4, 2017 UNLABELLED: Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordina ... Full text Link to item Cite

Disruption of Glucagon-Like Peptide 1 Signaling inSim1Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress

Journal Article The Journal of Neuroscience · January 4, 2017 Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating ... Full text Cite

One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer.

Journal Article Nat Biomed Eng · 2017 Stimulation of the glucagon-like peptide-1 (GLP1) receptor is a useful treatment strategy for type 2 diabetes because of pleiotropic effects, including the regulation of islet hormones and the induction of satiety. However, the native ligand for the GLP1 r ... Full text Link to item Cite

Baseline factors associated with glycaemic response to treatment with once-weekly dulaglutide in patients with type 2 diabetes.

Journal Article Diabetes Obes Metab · November 2016 Dulaglutide glycaemic efficacy has been demonstrated in the AWARD clinical trial programme. The objective of the present analysis was to determine the major baseline factors associated with the reduction in glycated haemoglobin (HbA1c) in response to dulag ... Full text Link to item Cite

Diabetes care: Lagniappe and seeing is believing!

Journal Article Diabetes Care · July 1, 2016 Full text Cite

Mechanisms of surgical control of type 2 diabetes: GLP-1 is the key factor-Maybe.

Journal Article Surg Obes Relat Dis · July 2016 Bariatric surgery is the most effective treatment for obesity and diabetes. The 2 most commonly performed weight-loss procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, improve glycemic control in patients with type 2 diabetes independent ... Full text Link to item Cite

Vitamin D status of black and white Americans and changes in vitamin D metabolites after varied doses of vitamin D supplementation.

Journal Article Am J Clin Nutr · July 2016 BACKGROUND: Controversy exists over the disparate circulating 25-hydroxyvitamin D [25(OH)D] concentrations between black and white Americans. OBJECTIVE: We sought to determine whether there are differences in total and directly measured free 25(OH)D concen ... Full text Link to item Cite

Bariatric Surgery: A Potential Treatment for Type 2 Diabetes in Youth.

Journal Article Diabetes Care · June 2016 Type 2 diabetes, once referred to as "adult-onset" diabetes, has now emerged as a formidable threat to the health of obese adolescents. Although there is growing evidence regarding the epidemiology of type 2 diabetes in youth and its multisystem health con ... Full text Link to item Cite

Ghrelin Impairs Prandial Glucose Tolerance and Insulin Secretion in Healthy Humans Despite Increasing GLP-1.

Journal Article J Clin Endocrinol Metab · June 2016 OBJECTIVES: Administration of ghrelin inhibits the acute insulin response to glucose and worsens IV glucose tolerance in healthy subjects. Evidence from preclinical studies suggests that ghrelin may have differential effects on glucose metabolism during fa ... Full text Link to item Cite

The incretin effect in obese adolescents with and without type 2 diabetes: impaired or intact?

Journal Article Am J Physiol Endocrinol Metab · May 1, 2016 The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction and described in T2D, IGT, and even obesity without IGT. We sought to d ... Full text Link to item Cite

Is GLP-1 a hormone: Whether and When?

Journal Article J Diabetes Investig · April 2016 Glucagon-like peptide-1 (GLP-1) is a product of proglucagon cleavage synthesized in L cells in the intestinal mucosa, α-cells in the pancreatic islet, and neurons in the nucleus of the solitary tract. GLP-1 is essential for normal glucose tolerance and act ... Full text Link to item Cite

Textbook of Diabetes

Chapter · 2016 Cite

Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus.

Journal Article Am J Clin Nutr · December 2015 BACKGROUND: A number of health benefits are associated with intake of soluble, viscous, gel-forming fibers, including reduced serum cholesterol and the attenuation of postprandial glucose excursions. OBJECTIVE: We assess the effects of psyllium, which is a ... Full text Link to item Cite

Insulin Sensitivity and β-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents.

Journal Article J Pediatr · November 2015 OBJECTIVE: To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). STUDY DESIGN: A longitudinal study of 22 adolescents and young adults without diabetes undergoing lapar ... Full text Link to item Cite

Mouse handling limits the impact of stress on metabolic endpoints.

Journal Article Physiol Behav · October 15, 2015 Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance ... Full text Link to item Cite

Gastric bypass alters both glucose-dependent and glucose-independent regulation of islet hormone secretion.

Journal Article Obesity (Silver Spring) · October 2015 OBJECTIVE: Roux-en-Y gastric bypass surgery (GB) is characterized by accentuated but short-lived postprandial elevations of blood glucose and insulin. This profile has been attributed to effects of relative hyperglycemia to directly stimulate β-cells and a ... Full text Link to item Cite

Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin.

Journal Article Diabetes · July 2015 Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insu ... Full text Link to item Cite

Exenatide Protects Against Glucose- and Lipid-Induced Endothelial Dysfunction: Evidence for Direct Vasodilation Effect of GLP-1 Receptor Agonists in Humans.

Journal Article Diabetes · July 2015 GLP-1 receptor (GLP-1R) agonists may improve endothelial function (EF) via metabolic improvement and direct vascular action. The current study determined the effect of GLP-1R agonist exenatide on postprandial EF in type 2 diabetes and the mechanisms underl ... Full text Link to item Cite

Diet-induced obese mice retain endogenous leptin action.

Journal Article Cell Metab · June 2, 2015 Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence ... Full text Link to item Cite

β-Cell Sensitivity to GLP-1 in Healthy Humans Is Variable and Proportional to Insulin Sensitivity.

Journal Article J Clin Endocrinol Metab · June 2015 CONTEXT: Glucagon-like peptide-1 (GLP-1) is an insulinotropic factor made in the gastrointestinal tract that is essential for normal glucose tolerance. Infusion of GLP-1 increases insulin secretion in both diabetic and nondiabetic humans. However, the degr ... Full text Link to item Cite

Ghrelin.

Journal Article Mol Metab · June 2015 BACKGROUND: The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regul ... Full text Open Access Link to item Cite

Physiology of proglucagon peptides: role of glucagon and GLP-1 in health and disease.

Journal Article Physiol Rev · April 2015 The preproglucagon gene (Gcg) is expressed by specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and a discrete set of neurons within the nucleus of the solitary tract. Gcg encodes multiple peptides including gluca ... Full text Link to item Cite

Rapid deterioration of insulin secretion in obese adolescents preceding the onset of type 2 diabetes.

Journal Article J Pediatr · March 2015 OBJECTIVE: To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents. STUDY DESIGN: Obese adolescents with normal glucose tolerance (n = 41) were studied longitudinally over the course of 4 years with serial measu ... Full text Link to item Cite

Ghrelin and hypothalamic development: too little and too much of a good thing.

Journal Article J Clin Invest · February 2015 Neural centers in the hypothalamus regulate food intake and body weight in response to hormones and other neural stimuli, and dysfunctional communication between the brain and gut underlies metabolic disorders, including obesity. In this issue of the JCI, ... Full text Link to item Cite

Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes.

Journal Article Diabetes Obes Metab · February 2015 AIM: To compare safety and efficacy of insulin glargine and liraglutide in patients with type 2 diabetes (T2DM). METHODS: This randomized, multinational, open-label trial included subjects treated for T2DM with metformin ± sulphonylurea, who had glycated h ... Full text Link to item Cite

Meal feeding improves oral glucose tolerance in male rats and causes adaptations in postprandial islet hormone secretion that are independent of plasma incretins or glycemia.

Journal Article Am J Physiol Endocrinol Metab · November 1, 2014 Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. W ... Full text Link to item Cite

Effects of glucagon like peptide-1 to mediate glycemic effects of weight loss surgery.

Journal Article Rev Endocr Metab Disord · September 2014 To date, weight loss surgeries are the most effective treatment for obesity and glycemic control in patients with type 2 diabetes. Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG), two widely used bariatric procedures for the treatment o ... Full text Link to item Cite

Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.

Journal Article Diabetes · July 2014 Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the ef ... Full text Open Access Link to item Cite

The role of β cell glucagon-like peptide-1 signaling in glucose regulation and response to diabetes drugs.

Journal Article Cell Metab · June 3, 2014 Glucagon-like peptide-1 (GLP-1), an insulinotropic gut peptide released after eating, is essential for normal glucose tolerance (GT). To determine whether this effect is mediated directly by GLP-1 receptors (GLP1R) on islet β cells, we developed mice with ... Full text Link to item Cite

Altered islet function and insulin clearance cause hyperinsulinemia in gastric bypass patients with symptoms of postprandial hypoglycemia.

Journal Article J Clin Endocrinol Metab · June 2014 CONTEXT: Postprandial hypoglycemia, a late complication of gastric bypass (GB) surgery, is associated with an exaggerated insulin response to meal ingestion. OBJECTIVE: The purpose of this study was to characterize insulin secretion and other glucoregulato ... Full text Link to item Cite

Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect.

Journal Article J Clin Invest · June 2014 Glucose control and weight loss are cornerstones of type 2 diabetes treatment. Currently, only glucagon-like peptide-1 (GLP1) analogs are able to achieve both weight loss and glucose tolerance. Both glucose and body weight are regulated by the brain, which ... Full text Link to item Cite

The effect of chronic twice daily exenatide treatment on β-cell function in new onset type 2 diabetes.

Journal Article Clin Endocrinol (Oxf) · April 2014 OBJECTIVE: To determine the effect of chronic daily exenatide treatment on β-cell function in type 2 diabetes (T2DM). BACKGROUND: Glucagon-like peptide receptor agonists, such as exenatide, are commonly used to treat patients with T2DM. Drugs in this class ... Full text Link to item Cite

Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

Journal Article Gastroenterology · March 2014 BACKGROUND & AIMS: Postprandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among patients with recurrent hypoglycemia. These patients also have increased postprandial levels of insulin and glucagon-like peptide 1 ... Full text Link to item Cite

Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy.

Journal Article Am J Physiol Endocrinol Metab · February 15, 2014 Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are effective weight loss surgeries that also improve glucose metabolism. Rapid, early rises of circulating insulin and glucagon-like peptide-1 (GLP-1) concentrations following food inge ... Full text Link to item Cite

GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.

Journal Article Diabetes · February 2014 Several bariatric operations are currently used to treat obesity and obesity-related comorbidities. These vary in efficacy, but most are more effective than current pharmaceutical treatments. Roux-en-Y gastric bypass (RYGB) produces substantial body weight ... Full text Link to item Cite

The role of the transcription factor ETV5 in insulin exocytosis.

Journal Article Diabetologia · February 2014 AIMS/HYPOTHESIS: Genome-wide association studies have revealed an association of the transcription factor ETS variant gene 5 (ETV5) with human obesity. However, its role in glucose homeostasis and energy balance is unknown. METHODS: Etv5 knockout (KO) mice ... Full text Link to item Cite

Effects of glucagon like peptide-1 to mediate glycemic effects of weight loss surgery

Journal Article Reviews in Endocrine and Metabolic Disorders · January 1, 2014 To date, weight loss surgeries are the most effective treatment for obesity and glycemic control in patients with type 2 diabetes. Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG), two widely used bariatric procedures for the treatment o ... Full text Cite

Improved glycemic control enhances the incretin effect in patients with type 2 diabetes.

Journal Article J Clin Endocrinol Metab · December 2013 BACKGROUND AND AIMS: Impairment of the incretin effect is one of the hallmarks of type 2 diabetes mellitus (T2DM). However, it is unknown whether this abnormality is specific to incretin-stimulated insulin secretion or a manifestation of generalized β-cell ... Full text Link to item Cite

High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.

Journal Article Circulation · November 26, 2013 BACKGROUND: Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increas ... Full text Link to item Cite

Cooperation between brain and islet in glucose homeostasis and diabetes.

Journal Article Nature · November 7, 2013 Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficie ... Full text Link to item Cite

Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice.

Journal Article Endocrinology · November 2013 Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, part ... Full text Link to item Cite

GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats.

Journal Article Diabetes · September 2013 Bariatric procedures vary in efficacy, but overall are more effective than behavioral and pharmaceutical treatment. Roux-en-Y gastric bypass causes increased secretion of glucagon-like peptide 1 (GLP-1) and reduces body weight (BW) more than adjustable gas ... Full text Link to item Cite

Impact of intestinal electrical stimulation on nutrient-induced GLP-1 secretion in vivo.

Journal Article Neurogastroenterol Motil · August 2013 BACKGROUND: Increases in L-cell release of GLP-1 are proposed to serve as a negative feedback signal for postprandial changes in gastric emptying and/or motility. Previous ex vivo data suggests that direct electrical stimulation (E-stim) of ileal segments ... Full text Link to item Cite

High-fat diet changes the temporal profile of GLP-1 receptor-mediated hypophagia in rats.

Journal Article Am J Physiol Regul Integr Comp Physiol · July 1, 2013 Overconsumption of a high-fat diet promotes weight gain that can result in obesity and associated comorbidities, including Type 2 diabetes mellitus. Consumption of a high-fat diet also alters gut-brain communication. Glucagon-like peptide 1 (GLP-1) is an i ... Full text Link to item Cite

The pharmacokinetics of acyl, des-acyl, and total ghrelin in healthy human subjects.

Journal Article Eur J Endocrinol · June 2013 BACKGROUND: Ghrelin stimulates GH secretion and regulates energy and glucose metabolism. The two circulating isoforms, acyl (AG) and des-acyl (DAG) ghrelin, have distinct metabolic effects and are under active investigation for their therapeutic potentials ... Full text Link to item Cite

Physiologic concentrations of exogenously infused ghrelin reduces insulin secretion without affecting insulin sensitivity in healthy humans.

Journal Article J Clin Endocrinol Metab · June 2013 BACKGROUND: Infusion of ghrelin to supraphysiologic levels inhibits glucose-stimulated insulin secretion, reduces insulin sensitivity, and worsens glucose tolerance in humans. OBJECTIVE: The purpose of this study was to determine the effects of lower doses ... Full text Link to item Cite

Fibroblast growth factor 21 mediates specific glucagon actions.

Journal Article Diabetes · May 2013 Glucagon, an essential regulator of glucose homeostasis, also modulates lipid metabolism and promotes weight loss, as reflected by the wasting observed in glucagonoma patients. Recently, coagonist peptides that include glucagon agonism have emerged as prom ... Full text Link to item Cite

Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats.

Journal Article Endocrinology · March 2013 Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whethe ... Full text Link to item Cite

Investigation of the mechanisms contributing to the compensatory increase in insulin secretion during dexamethasone-induced insulin resistance in rhesus macaques.

Journal Article J Endocrinol · February 2013 Dexamethasone has well-described effects to induce insulin resistance and increase insulin secretion. Herein, we examined potential contributors to the effect of dexamethasone to increase insulin secretion in rhesus macaques. Six male rhesus macaques recei ... Full text Link to item Cite

One-year sustained glycemic control and weight reduction in type 2 diabetes after addition of liraglutide to metformin followed by insulin detemir according to HbA1c target.

Journal Article J Diabetes Complications · 2013 AIM: To investigate durability of efficacy and safety over 1 year of the sequence of liraglutide added to metformin followed by add-on insulin detemir if glycated hemoglobin (HbA1c) remains ≥7.0%. METHODS: Patients previously uncontrolled on metformin±sulf ... Full text Link to item Cite

Suppression of food intake by glucagon-like peptide-1 receptor agonists: relative potencies and role of dipeptidyl peptidase-4.

Journal Article Endocrinology · December 2012 Administration of the glucagon-like peptide-1 (GLP-1) receptor agonists GLP-1 and exendin-4 (Ex-4) directly into the central nervous system decreases food intake. But although Ex-4 potently suppresses food intake after peripheral administration, the effect ... Full text Link to item Cite

Effect of glycemia on plasma incretins and the incretin effect during oral glucose tolerance test.

Journal Article Diabetes · November 2012 The incretin effect, reflecting the enhancement of postprandial insulin secretion by factors including the intestinal hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, increases in proportion to meal size. However, ... Full text Link to item Cite

Effect of vertical sleeve gastrectomy on food selection and satiation in rats.

Journal Article Am J Physiol Endocrinol Metab · October 15, 2012 Vertical sleeve gastrectomy (VSG) is a restrictive procedure that reduces food intake to produce weight loss. Here we assess volume and nutrient effects on the ingestive behavior of VSG and sham surgery animals. Rats given access to Ensure or pelleted chow ... Full text Link to item Cite

Ghrelin stimulation of growth hormone isoforms: parallel secretion of total and 20-kDa growth hormone and relation to insulin sensitivity in healthy humans.

Journal Article J Clin Endocrinol Metab · September 2012 CONTEXT: The 20-kDa human GH (hGH) is produced in the pituitary by alternative splicing of the hGH-N gene. The 20-kDa hGH promotes growth similarly to 22-kDa or total hGH, the predominant form in circulation, but the relative effects of these isoforms on g ... Full text Link to item Cite

Role of carbohydrate modification in weight management among obese children: a randomized clinical trial.

Journal Article J Pediatr · August 2012 OBJECTIVE: To compare the effectiveness and safety of carbohydrate (CHO)-modified diets with a standard portion-controlled (PC) diet in obese children. STUDY DESIGN: Obese children (n=102) aged 7-12 years were randomly assigned to a 3-month intervention of ... Full text Link to item Cite

Insulin increases central apolipoprotein E levels as revealed by an improved technique for collection of cerebrospinal fluid from rats.

Journal Article J Neurosci Methods · July 30, 2012 Cerebrospinal fluid (CSF) provides an invaluable analytical window to the central nervous system (CNS) because it reflects the dynamically changing complement of CNS constituents. We describe an improved method for sampling CSF in rats that is easy to perf ... Full text Link to item Cite

Effect of vertical sleeve gastrectomy in melanocortin receptor 4-deficient rats.

Journal Article Am J Physiol Endocrinol Metab · July 1, 2012 Bariatric surgery is currently the most effective treatment for obesity. Vertical sleeve gastrectomy (VSG), a commonly applied bariatric procedure, involves surgically incising most of the volume of the stomach. In humans, partial loss of melanocortin rece ... Full text Link to item Cite

Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin prompted by A1C targets.

Journal Article Diabetes Care · July 2012 OBJECTIVE: We evaluated the addition of liraglutide to metformin in type 2 diabetes followed by intensification with basal insulin (detemir) if glycated hemoglobin (A1C) ≥7%. RESEARCH DESIGN AND METHODS: In 988 participants from North America and Europe un ... Full text Link to item Cite

β-cell dysfunction in adolescents and adults with newly diagnosed type 2 diabetes mellitus.

Journal Article J Pediatr · June 2012 OBJECTIVE: To compare β-cell function in adolescents and adults with newly diagnosed type 2 diabetes (T2DM). STUDY DESIGN: Thirty-nine adolescents with T2DM, 38 age- and weight-matched control subjects, and 19 adults with T2DM were studied. The adolescent ... Full text Link to item Cite

Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP.

Journal Article Lipids · June 2012 Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins produced in the intestine that play a central role in glucose metabolism and insulin secretion. Circulating concentrations of GLP-1 and GIP are low and can ... Full text Link to item Cite

Multiparity leads to obesity and inflammation in mothers and obesity in male offspring.

Journal Article Am J Physiol Endocrinol Metab · February 15, 2012 Multiparity is an independent risk factor for obesity in parous females. In addition to being a health issue for the mother, offspring of multiparous females may also be at risk for obesity later in life. The aim of the current study was to establish a mou ... Full text Link to item Cite

The anorectic effect of GLP-1 in rats is nutrient dependent.

Journal Article PLoS One · 2012 GLP-1-induced insulin secretion from the β-cell is dependent upon glucose availability. The purpose of the current study was to determine whether CNS GLP-1 signaling is also glucose-dependent. We found that fasting blunted the ability of 3(rd) cerebroventr ... Full text Link to item Cite

Similar effects of roux-en-Y gastric bypass and vertical sleeve gastrectomy on glucose regulation in rats.

Journal Article Physiol Behav · November 30, 2011 Bariatric surgery is the most efficacious procedure for eliciting weight loss in humans, and many patients undergoing the procedure experience significant lessening of their symptoms of type-2 diabetes in addition to losing weight. We have adapted two bari ... Full text Link to item Cite

Adiponectin changes in relation to the macronutrient composition of a weight-loss diet.

Journal Article Obesity (Silver Spring) · November 2011 Adiponectin is an adipose-derived protein with beneficial metabolic effects. Low adiponectin is associated with obesity and related diseases. Significant weight loss increases adiponectin, reducing disease risk. This study compared the effects of two weigh ... Full text Link to item Cite

The role of dysregulated glucagon secretion in type 2 diabetes.

Journal Article Diabetes Obes Metab · October 2011 Excessive production of glucose by the liver contributes to fasting and postprandial hyperglycaemia, hallmarks of type 2 diabetes. A central feature of this pathologic response is insufficient hepatic insulin action, due to a combination of insulin resista ... Full text Link to item Cite

Contributions of fat and protein to the incretin effect of a mixed meal.

Journal Article Am J Clin Nutr · October 2011 BACKGROUND: The relative contributions of fat and protein to the incretin effect are still largely unknown. OBJECTIVE: This study assessed the incretin effects elicited by a mixed meal, and by its fat and protein components alone, with the use of a hypergl ... Full text Link to item Cite

Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats.

Journal Article Gastroenterology · September 2011 BACKGROUND & AIMS: Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) reduce weight and improve glucose metabolism in obese patients, although it is not clear if metabolic changes are independent of weight loss. We investigated alteratio ... Full text Link to item Cite

Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans.

Journal Article Diabetes · September 2011 OBJECTIVE: Gastric bypass (GB) surgery is associated with postprandial hyperinsulinemia, and this effect is accentuated in postsurgical patients who develop recurrent hypoglycemia. Plasma levels of the incretin glucagon-like peptide 1 (GLP-1) are dramatica ... Full text Link to item Cite

Impaired insulin secretion and enhanced insulin sensitivity in cholecystokinin-deficient mice.

Journal Article Diabetes · July 2011 OBJECTIVE: Cholecystokinin (CCK) is released in response to lipid intake and stimulates insulin secretion. We hypothesized that CCK deficiency would alter the regulation of insulin secretion and glucose homeostasis. RESEARCH DESIGN AND METHODS: We used qua ... Full text Link to item Cite

GLP-1 and energy balance: an integrated model of short-term and long-term control.

Journal Article Nat Rev Endocrinol · June 7, 2011 Glucagon-like peptide 1 (GLP-1), a peptide secreted from the intestine in response to nutrient ingestion, is perhaps best known for its effect on glucose-stimulated insulin secretion. GLP-1 is also secreted from neurons in the caudal brainstem, and it is w ... Full text Link to item Cite

Consumption of a high-fat diet induces central insulin resistance independent of adiposity.

Journal Article Physiol Behav · April 18, 2011 Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central ... Full text Link to item Cite

Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans.

Journal Article J Neurosci · April 13, 2011 Olfaction is an integral part of feeding providing predictive cues that anticipate ingestion. Although olfactory function is modulated by factors such as prolonged fasting, the underlying neural mechanisms remain poorly understood. We recently identified g ... Full text Link to item Cite

Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function.

Journal Article J Neurosci · March 9, 2011 Central administration of glucagon-like peptide-1 (GLP-1) causes a dose-dependent reduction in food intake, but the role of endogenous CNS GLP-1 in the regulation of energy balance remains unclear. Here, we tested the hypothesis that CNS GLP-1 activity is ... Full text Link to item Cite

Bypassing the duodenum does not improve insulin resistance associated with diet-induced obesity in rodents.

Journal Article Obesity (Silver Spring) · February 2011 Roux-en-y gastric bypass (RYGB) surgery rapidly improves glucose tolerance and reverses insulin resistance in obese patients. It has been hypothesized that this effect is mediated by the diversion of nutrients from the proximal small intestine. We utilized ... Full text Link to item Cite

Eating disorders and gastrointestinal peptides.

Journal Article Curr Opin Endocrinol Diabetes Obes · February 2011 PURPOSE OF REVIEW: Disturbances in gastrointestinal hormones have been implicated in the pathogenesis of eating disorders such as anorexia nervosa and bulimia nervosa. However, the contribution of these hormonal changes to the onset and maintenance of eati ... Full text Link to item Cite

Environmental changes to control obesity: a randomized controlled trial in manufacturing companies.

Journal Article Am J Health Promot · 2011 PURPOSE: To determine the effects of an environmental intervention on obesity, disease risk factors, and dietary intake in an employee population. DESIGN: Randomized controlled community trial. SETTING: Eight manufacturing companies in Kentucky with ∼150 t ... Full text Link to item Cite

Role of glucocorticoids in tuning hindbrain stress integration.

Journal Article J Neurosci · November 3, 2010 The nucleus of the solitary tract (NTS) is a critical integrative site for coordination of autonomic and endocrine stress responses. Stress-excitatory signals from the NTS are communicated by both catecholaminergic [norepinephrine (NE), epinephrine (E)] an ... Full text Link to item Cite

Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities.

Journal Article Am J Physiol Gastrointest Liver Physiol · September 2010 Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Ou ... Full text Link to item Cite

Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.

Journal Article Diabetes · September 2010 OBJECTIVE: The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test t ... Full text Open Access Link to item Cite

Impaired beta-cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes.

Journal Article Pediatr Diabetes · August 2010 BACKGROUND: Adults with type 2 diabetes mellitus (T2DM) have broad impairments in beta-cell function, including severe attenuation of the first-phase insulin response to glucose, and reduced beta-cell mass. In adolescents with T2DM, there is some evidence ... Full text Link to item Cite

Editorial introductions

Journal Article Current Opinion in Clinical Nutrition and Metabolic Care · July 1, 2010 Full text Cite

Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes.

Journal Article Diabetes · June 2010 OBJECTIVE: The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) account for up to 60% of postprandial insulin release in healthy people. Previous studies showed a reduced incretin effect in patients with type ... Full text Link to item Cite

The contribution of enteroinsular hormones to the pathogenesis of type 2 diabetes mellitus.

Journal Article Curr Diab Rep · June 2010 The gastrointestinal hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), termed incretins, are essential regulators of normal glucose homeostasis. Research indicates that the incretin effect is impaired in type ... Full text Link to item Cite

The effect of duodenal-jejunal bypass on glucose-dependent insulinotropic polypeptide secretion in Wistar rats.

Journal Article Obes Surg · June 2010 BACKGROUND: Enteroendocrine K cells secrete the incretin hormone glucose-dependent insulinotropic peptide (GIP) and are predominately located in the duodenum. GIP levels should decrease after gastric bypass due to duodenal exclusion; however, studies have ... Full text Link to item Cite

Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system.

Journal Article Am J Physiol Endocrinol Metab · May 2010 Exendin-4 (Ex-4), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Bec ... Full text Link to item Cite

The intestinal lymph fistula model--a novel approach to study ghrelin secretion.

Journal Article Am J Physiol Gastrointest Liver Physiol · March 2010 The orexigenic hormone ghrelin is secreted from the stomach and has been implicated in the regulation of energy and glucose homeostasis. We hypothesized that ghrelin, like other gastrointestinal (GI) hormones, is present in intestinal lymph, and sampling t ... Full text Link to item Cite

Meal-anticipatory glucagon-like peptide-1 secretion in rats.

Journal Article Endocrinology · February 2010 Animals anticipating a meal initiate a series of responses enabling them to better cope with the meal's metabolic impact. These responses, such as cephalic insulin, occur prior to the onset of ingestion and are especially evident in animals maintained on a ... Full text Link to item Cite

Differences in the central anorectic effects of glucagon-like peptide-1 and exendin-4 in rats.

Journal Article Diabetes · December 2009 OBJECTIVE: Glucagon-like peptide (GLP)-1 is a regulatory peptide synthesized in the gut and the brain that plays an important role in the regulation of food intake. Both GLP-1 and exendin (Ex)-4, a long-acting GLP-1 receptor (GLP-1r) agonist, reduce food i ... Full text Link to item Cite

Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis.

Journal Article Crit Care Med · December 2009 OBJECTIVES: Hyperglycemia during critical illness is common and is associated with increased mortality. Intensive insulin therapy has improved outcomes in some, but not all, intervention trials. It is unclear whether the benefits of treatment differ among ... Full text Link to item Cite

Duodenal-jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism.

Journal Article J Gastrointest Surg · October 2009 BACKGROUND: Gastric bypass results in the rapid resolution of type 2 diabetes. No causal evidence exists to link specific gut hormone changes with improvements in glucose homeostasis post-operatively. We hypothesized that surgical augmentation of the gluco ... Full text Link to item Cite

Gender differences in the relationships among obesity, adiponectin and brachial artery distensibility in adolescents and young adults.

Journal Article Int J Obes (Lond) · October 2009 BACKGROUND: Obesity-related cardiovascular diseases (CVDs) are a major cause of cardiovascular (CV) mortality. Obesity-related reduction in vascular protective adipose-derived proteins, such as adiponectin (APN), has an important role. METHODS: We compared ... Full text Link to item Cite

Impaired proinsulin processing is a characteristic of transplanted islets.

Journal Article Am J Transplant · September 2009 We sought to determine whether recipients of islet transplants have defective proinsulin processing. Individuals who had islet allo- or autotransplantation were compared to healthy nondiabetic subjects. Insulin (I), total proinsulin (TP), intact proinsulin ... Full text Link to item Cite

Food intake-independent effects of CB1 antagonism on glucose and lipid metabolism.

Journal Article Obesity (Silver Spring) · August 2009 Overactivity of the endocannabinoid system (ECS) has been linked to abdominal obesity and other risk factors for cardiovascular disease and type 2 diabetes. Conversely, administration of cannabinoid receptor type 1 (CB1) antagonists reduces adiposity in ob ... Full text Link to item Cite

Editorial introductions

Journal Article Current Opinion in Clinical Nutrition and Metabolic Care · July 1, 2009 Full text Cite

The effects of GLP-1 infusion in the hepatic portal region on food intake.

Journal Article Regul Pept · June 5, 2009 A wide range of evidence points to a role for GLP-1 to regulate food intake. Anorectic effects of GLP-1 are most apparent when the peptide is administered directly into the central nervous system (CNS), but suppression of food intake has also been noted in ... Full text Link to item Cite

Glucocorticoid regulation of preproglucagon transcription and RNA stability during stress.

Journal Article Proc Natl Acad Sci U S A · April 7, 2009 Stress elicits a synchronized response of the endocrine, sympathetic, and central nervous systems to preserve homeostasis and well-being. Glucagon-like peptide-1 (GLP-1), a primary posttranslational product of the preproglucagon (PPG) gene, activates both ... Full text Link to item Cite

One-year comparison of a high-monounsaturated fat diet with a high-carbohydrate diet in type 2 diabetes.

Journal Article Diabetes Care · February 2009 OBJECTIVE: The purpose of this study was to compare the effects of high-monounsaturated fatty acid (MUFA) and high-carbohydrate (CHO) diets on body weight and glycemic control in men and women with type 2 diabetes. RESEARCH DESIGN AND METHODS: Overweight/o ... Full text Link to item Cite

Tetrahydroindenoindole inhibits the progression of diabetes in mice.

Journal Article Chem Biol Interact · January 15, 2009 Diabetes is characterized by elevated fasting blood glucose (FBG) resulting from improper insulin regulation and/or insulin resistance. Herein we used female C57BL/6J mouse models for type 1 diabetes (streptozotocin [STZ] treatment) and type 2 diabetes (hi ... Full text Link to item Cite

Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes.

Journal Article J Clin Endocrinol Metab · January 2009 CONTEXT: Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide ... Full text Link to item Cite

Distribution of glucagon-like peptide-1 immunoreactivity in the hypothalamic paraventricular and supraoptic nuclei.

Journal Article J Chem Neuroanat · December 2008 Glucagon-like peptide-1 (GLP-1) plays a role in modulating neuroendocrine and autonomic function. The hypothalamic paraventricular nucleus (PVN) contains aggregations of GLP-1 fibers and expresses GLP-1 receptors, making it a likely site of action for GLP- ... Full text Link to item Cite

Regulation of islet hormone release and gastric emptying by endogenous glucagon-like peptide 1 after glucose ingestion.

Journal Article J Clin Endocrinol Metab · December 2008 BACKGROUND: Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the ... Full text Link to item Cite

Central control of body weight and appetite.

Journal Article J Clin Endocrinol Metab · November 2008 CONTEXT: Energy balance is critical for survival and health, and control of food intake is an integral part of this process. This report reviews hormonal signals that influence food intake and their clinical applications. EVIDENCE ACQUISITION: A relatively ... Full text Link to item Cite

Benefits of high-protein weight loss diets: enough evidence for practice?

Journal Article Curr Opin Endocrinol Diabetes Obes · October 2008 PURPOSE OF REVIEW: High-protein diets, often with carbohydrate restriction, are quite popular among overweight Americans pursuing strategies for weight control. Recently, well designed clinical trials have evaluated the anthropometric and metabolic effects ... Full text Link to item Cite

A sweet spot for the bariatric surgeon.

Journal Article Cell Metab · September 2008 While gastric bypass surgery remains popular as the only treatment for morbid obesity with curative potential, the molecular mechanisms underpinning its immediate metabolic benefits remain unclear. New work in this issue (Troy et al., 2008) suggests intest ... Full text Link to item Cite

Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake.

Journal Article Diabetes · August 2008 OBJECTIVE: Glucagon-like peptide-1 (GLP-1) promotes glucose homeostasis through regulation of islet hormone secretion, as well as hepatic and gastric function. Because GLP-1 is also synthesized in the brain, where it regulates food intake, we hypothesized ... Full text Link to item Cite

Abnormalities in glucose tolerance are common in children with fanconi anemia and associated with impaired insulin secretion.

Journal Article Pediatr Blood Cancer · August 2008 BACKGROUND: To determine prevalence of abnormal glucose metabolism in Fanconi Anemia (FA). PROCEDURE: Thirty-nine children with FA underwent 2-hr oral glucose tolerance test (OGTT). Reference lean adolescents (REF) were older than FA patients (mean +/- SD: ... Full text Link to item Cite

Randy J Seeley

Journal Article JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM · August 1, 2008 Link to item Cite

Dr. Randy J. Seeley

Journal Article ENDOCRINOLOGY · August 1, 2008 Link to item Cite

Failure of glucagon-like peptide-1 to induce panic attacks or anxiety in patients with panic disorder.

Journal Article J Psychiatr Res · July 2008 The insulin secretogogue glucagon like peptide-1 (GLP-1), as well as agents which enhance GLP-1 signaling, are being studied as potential treatments for diabetes. Pre-clinical evidence suggests that these agents may have neuropsychiatric side effects; howe ... Full text Link to item Cite

Targeting beta-cell mass in type 2 diabetes: promise and limitations of new drugs based on incretins.

Journal Article Endocr Rev · May 2008 Progressive insulin secretory defects, due to either functional abnormalities of the pancreatic beta-cells or a reduction in beta-cell mass, are the cornerstone of type 2 diabetes. Incretin-based drugs hold the potential to improve glucose tolerance by imm ... Full text Link to item Cite

Using the lymph fistula rat model to study the potentiation of GIP secretion by the ingestion of fat and glucose.

Journal Article Am J Physiol Gastrointest Liver Physiol · May 2008 Glucose-dependent insulinotropic polypeptide (GIP) is an important incretin produced in the K cells of the intestine and secreted into the circulating blood following ingestion of carbohydrate- and fat-containing meals. GIP contributes to the regulation of ... Full text Link to item Cite

Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low-fat but not a low-carbohydrate diet in obese women.

Journal Article Metabolism · April 2008 Although circulating glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor high-density lipoprotein-associated protein, is elevated in patients with insulin resistance or high triglycerides, no information is available on the effect of w ... Full text Link to item Cite

Mice with chronically increased circulating ghrelin develop age-related glucose intolerance.

Journal Article Am J Physiol Endocrinol Metab · April 2008 Ghrelin is a gut peptide that stimulates food intake and increases body fat mass when administered centrally or peripherally. In this study, ghrelin was overexpressed in neurons using the neuron-specific enolase (NSE) promoter sequences and mouse ghrelin c ... Full text Link to item Cite

Role of central glucagon-like peptide-1 in hypothalamo-pituitary-adrenocortical facilitation following chronic stress.

Journal Article Exp Neurol · April 2008 Central glucagon-like peptide-1 (GLP-1) regulates food intake, glucose homeostasis, and behavioral and neuroendocrine responses to acute stress. Given its pronounced role in acute stress regulation, the GLP-1 system is a prime candidate for mediating the p ... Full text Link to item Cite

Voluntary consumption of ethyl oleate reduces food intake and body weight in rats.

Journal Article Physiol Behav · March 18, 2008 Previous studies have shown that administration of the fatty acids, linoleic and oleic acid, either by intragastric or intraintestinal infusion, suppresses food intake and body weight in rats. While still not fully understood, gut-mediated satiety mechanis ... Full text Link to item Cite

Acetaminophen normalizes glucose homeostasis in mouse models for diabetes.

Journal Article Biochem Pharmacol · March 15, 2008 Loss of pancreatic beta cell insulin secretion is the most important element in the progression of type 1 and type 2 diabetes. Since oxidative stress is involved in the progressive loss of beta cell function, we evaluated the potential for the over-the-cou ... Full text Link to item Cite

Weight loss and metabolic benefits with diets of varying fat and carbohydrate content: separating the wheat from the chaff.

Journal Article Nat Clin Pract Endocrinol Metab · March 2008 With the rising prevalence of both obesity and diabetes, the contributing role of diet to the prevention and treatment of these conditions has become a major focus of research, clinical practice, and public policy. There has been intense debate over which ... Full text Link to item Cite

Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release.

Journal Article Obesity (Silver Spring) · February 2008 BACKGROUND: Bariatric surgery markedly improves glucose homeostasis in patients with type 2 diabetes even before any significant weight loss is achieved. Procedures that involve bypassing the proximal small bowel, such as Roux-en-Y gastric bypass (RYGBP), ... Full text Link to item Cite

High-dose escitalopram in the treatment of binge-eating disorder with obesity: a placebo-controlled monotherapy trial.

Journal Article Hum Psychopharmacol · January 2008 OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of high-dose escitalopram in the treatment of binge-eating disorder (BED) associated with obesity. METHOD: Forty-four outpatients with BED by DSM-IV criteria and obesity were rand ... Full text Link to item Cite

Intestinal hormones and regulation of satiety: the case for CCK, GLP-1, PYY, and Apo A-IV.

Conference JPEN J Parenter Enteral Nutr · 2008 Satiety, the physiologic processes that combine to bring about the cessation of a meal, is controlled in part by intestinal peptide secretion. The effects of cholecystokinin, glucagon-like peptide I, peptide YY, and apolipoprotein A-IV are described. ... Full text Link to item Cite

Glucose tolerance, insulin secretion, and insulin sensitivity in children and adolescents with cystic fibrosis and no prior history of diabetes.

Journal Article J Pediatr · December 2007 OBJECTIVE: To determine the prevalence of abnormalities of glucose metabolism in pediatric outpatients with cystic fibrosis (CF). STUDY DESIGN: Children and adolescents (n = 73, mean age 15.0 +/- 3.7 years) with CF not previously diagnosed with diabetes un ... Full text Link to item Cite

Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system.

Journal Article Am J Physiol Regul Integr Comp Physiol · December 2007 Glucagon like peptide 1 (GLP-1) is an intestinal hormone that plays an important role in glucose metabolism. GLP-1 is released from mucosal L cells following nutrient ingestion and contributes to the incretin effect, with the enhancement of insulin secreti ... Full text Link to item Cite

The regulation of the lymphatic secretion of glucagon-like peptide-1 (GLP-1) by intestinal absorption of fat and carbohydrate.

Journal Article Am J Physiol Gastrointest Liver Physiol · November 2007 Glucagon-like peptide-1 (GLP-1) is an important incretin produced in the L cells of the intestine. It is essential in the regulation of insulin secretion and glucose homeostasis. Systemic GLP-1 concentrations are typically low in rodents, so it can be diff ... Full text Link to item Cite

Glucagon-like peptide-1 (GLP-1) receptors expressed on nerve terminals in the portal vein mediate the effects of endogenous GLP-1 on glucose tolerance in rats.

Journal Article Endocrinology · October 2007 Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that is secreted during meal absorption and is essential for normal glucose homeostasis. However, the relatively low plasma levels and rapid metabolism of GLP-1 raise questions as to whether direct e ... Full text Link to item Cite

Prevalence of obesity and cardiovascular risk factors among manufacturing company employees in Kentucky.

Journal Article AAOHN J · October 2007 The purpose of this study was to examine the prevalence of obesity and cardiovascular risk factors among male and female employees of eight small manufacturing companies in Kentucky. Randomly selected employees were screened using anthropometric and metabo ... Full text Link to item Cite

Ghrelin, obesity and diabetes.

Journal Article Nat Clin Pract Endocrinol Metab · October 2007 The high prevalence of obesity and diabetes will lead to higher rates of morbidity and mortality. The search for drugs to treat these metabolic disorders has, therefore, intensified. The stomach-derived peptide ghrelin regulates food intake and body weight ... Full text Link to item Cite

Editorial introductions

Journal Article Current Opinion in Clinical Nutrition and Metabolic Care · July 1, 2007 Full text Cite

Overweight and hyperinsulinemia provide individual contributions to compromises in brachial artery distensibility in healthy adolescents and young adults

Journal Article Journal of the American Society of Hypertension · May 1, 2007 Brachial artery distensibility (BrachD) was measured in healthy children to identify associations with atherosclerotic risk factors. Nine hundred sixty-nine black and white subjects, 13-22 years of age, were classified as lean (L) or overweight (O) and as ... Full text Cite

Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.

Journal Article J Clin Endocrinol Metab · February 2007 BACKGROUND: Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the ... Full text Link to item Cite

Glucagon-like peptide 1: continued advances, new targets and expanding promise as a model therapeutic.

Journal Article Curr Opin Endocrinol Diabetes Obes · February 2007 PURPOSE OF REVIEW: This article discusses glucagon-like peptide 1 physiology and its various sites of action beyond the incretin effect and highlights recent findings (2005 and 2006). RECENT FINDINGS: Glucagon-like peptide 1 is a physiological incretin in ... Full text Link to item Cite

Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial.

Journal Article J Clin Psychiatry · December 2006 OBJECTIVE: Binge eating disorder (BED) is associated with obesity. Zonisamide is a novel antiepileptic drug associated with weight loss. The purpose of this study was to evaluate zonisa-mide in the treatment of BED associated with obesity. METHOD: In this ... Full text Link to item Cite

Type 2 diabetes, thiazolidinediones: bad to the bone?

Journal Article J Clin Endocrinol Metab · September 2006 Full text Link to item Cite

Editorial introductions

Journal Article Current Opinion in Clinical Nutrition and Metabolic Care · July 1, 2006 Full text Cite

Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1.

Journal Article Cell Metab · June 2006 Nutrient overload leads to obesity, insulin resistance, and often type 2 diabetes. Whereas increased fat intake is commonly cited as the major factor in diet-induced dysmetabolic states, increased protein consumption also contributes, through elevated circ ... Full text Link to item Cite

New therapies for type 2 diabetes based on glucagon-like peptide 1.

Journal Article Cleve Clin J Med · April 2006 Cells in the gastrointestinal tract secrete several hormones that stimulate insulin secretion, one of which is glucagon-like peptide (GLP-1). Several new drugs act through the GLP-1 signaling system to stimulate insulin release and regulate blood glucose l ... Full text Link to item Cite

Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status.

Journal Article Endocrinology · January 2006 Circulating levels of the orexigenic peptide ghrelin increase during fasting and decrease with refeeding. Exogenous ghrelin administration is a potent stimulus for food intake in rodents and humans. In subjects on fixed feeding schedules, ghrelin increases ... Full text Link to item Cite

Beta-cell function, insulin sensitivity, and glucose tolerance in obese diabetic and nondiabetic adolescents and young adults.

Journal Article J Clin Endocrinol Metab · January 2006 CONTEXT: Type 2 diabetes mellitus (T2DM) is estimated to account for 10-45% of incident pediatric diabetes cases. OBJECTIVE: Our objective was to characterize the metabolic defects underlying T2DM in adolescents and young adults. DESIGN, SETTING, AND PATIE ... Full text Link to item Cite

Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake.

Journal Article Am J Physiol Regul Integr Comp Physiol · January 2006 Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine whether apo A-IV interacts with the central melanocortin (MC) system in the control of feedin ... Full text Link to item Cite

New ways in which GLP-1 can regulate glucose homeostasis.

Journal Article J Clin Invest · December 2005 Glucagon-like peptide-1 (GLP-1) has a diverse set of peripheral actions which all serve to promote enhanced glucose tolerance, and for this reason it has become the basis for new treatments for type 2 diabetes. In this issue of the JCI, Knauf et al. provid ... Full text Link to item Cite

Comparative analysis of ACTH and corticosterone sampling methods in rats.

Journal Article Am J Physiol Endocrinol Metab · November 2005 A frequently debated question for studies involving the measurement of stress hormones in rodents is the optimal method for collecting blood with minimal stress to the animal. Some investigators prefer the implantation of indwelling catheters to allow for ... Full text Link to item Cite

Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis.

Journal Article J Am Coll Surg · November 2005 BACKGROUND: For patients who suffer from severe chronic pancreatitis, total pancreatectomy can alleviate pain, and islet autotransplantation (IAT) might preserve endocrine function and circumvent the complications of diabetes. Factors that determine succes ... Full text Link to item Cite

Utilizing the GLP-1 signaling system to treat diabetes: sorting through the pharmacologic approaches.

Journal Article Curr Diab Rep · October 2005 Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that promotes glucose homeostasis through the regulation of insulin and glucagon secretion, gastric emptying, and food intake. This spectrum of effects makes GLP-1 an attractive candidate for drug de ... Full text Link to item Cite

Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity.

Journal Article Am J Physiol Regul Integr Comp Physiol · September 2005 Oleoylethanolamide (OEA), a lipid synthesized in the intestine, reduces food intake and stimulates lipolysis through peroxisome proliferator-activated receptor-alpha. OEA also activates transient receptor potential vanilloid type 1 (TRPV1) in vitro. Becaus ... Full text Link to item Cite

Type 2 diabetes and insulin resistance: an hepatocentric phenomenon?

Journal Article Curr Opin Clin Nutr Metab Care · July 2005 Full text Link to item Cite

Frequency of abnormal carbohydrate metabolism and diabetes in a population-based screening of adolescents.

Journal Article J Pediatr · June 2005 OBJECTIVE: To document the frequency of glucose intolerance in adolescents in a population-based study of primarily African-American/Non-Hispanic whites in an urban-suburban school district. STUDY DESIGN: Measurement of fasting and 2-hour post-glucose load ... Full text Link to item Cite

GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats.

Journal Article Am J Physiol Gastrointest Liver Physiol · May 2005 Glucagon-like peptide 1 (GLP-1) is a gastrointestinal hormone secreted in response to meal ingestion by enteroendocrine L cells located predominantly in the lower small intestine and large intestine. GLP-1 inhibits the secretion and motility of the upper g ... Full text Link to item Cite

Diet-induced weight loss is associated with decreases in plasma serum amyloid a and C-reactive protein independent of dietary macronutrient composition in obese subjects.

Journal Article J Clin Endocrinol Metab · April 2005 Elevated levels of serum amyloid A (SAA) and C-reactive protein (CRP) have been associated with increased cardiovascular risk. Although levels of CRP decrease with weight loss, it is not known whether SAA decreases with weight loss or whether dietary macro ... Full text Link to item Cite

The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets.

Journal Article J Clin Endocrinol Metab · March 2005 We have recently reported that obese women randomized to a low-carbohydrate diet lost more than twice as much weight as those following a low-fat diet over 6 months. The difference in weight loss was not explained by differences in energy intake because wo ... Full text Link to item Cite

Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats.

Journal Article Am J Physiol Endocrinol Metab · February 2005 Bariatric surgeries, such as gastric bypass, result in dramatic and sustained weight loss that is usually attributed to a combination of gastric volume restriction and intestinal malabsorption. However, studies parceling out the contribution of enhanced in ... Full text Link to item Cite

Clinical significance of bacterial cultures from 28 autologous islet cell transplant solutions.

Journal Article Pancreatology · 2005 PURPOSE: Total pancreatectomy and autologous islet cell transplantation are being investigated as a novel surgical treatment for patients with chronic pancreatitis. Preliminary data has demonstrated the presence of enteric bacteria in solutions used to har ... Full text Link to item Cite

The role of central glucagon-like peptide-1 in mediating the effects of visceral illness: differential effects in rats and mice.

Journal Article Endocrinology · January 2005 In rats, central administration of glucagon-like peptide-1 (GLP-1) elicits symptoms of visceral illness like those caused by the toxin lithium chloride (LiCl), including anorexia, conditioned taste aversion (CTA) formation, and neural activation in the hyp ... Full text Link to item Cite

Consumption of a high-fat diet alters the homeostatic regulation of energy balance.

Journal Article Physiol Behav · December 30, 2004 Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psycholog ... Full text Link to item Cite

Obesity induced by a high-fat diet downregulates apolipoprotein A-IV gene expression in rat hypothalamus.

Journal Article Am J Physiol Endocrinol Metab · August 2004 Apolipoprotein A-IV (apo A-IV) is an anorectic protein produced in the intestine and brain that has been proposed as a satiety signal. To determine whether diet-induced obesity alters apo A-IV gene expression in the intestine and hypothalamus, rats were fe ... Full text Link to item Cite

Editorial introductions

Journal Article Current Opinion in Clinical Nutrition and Metabolic Care · July 1, 2004 Full text Cite

How are we going to understand (dys)regulation of glucose metabolism?

Journal Article Curr Opin Clin Nutr Metab Care · July 2004 Full text Link to item Cite

Glucagon-like peptide 1: evolution of an incretin into a treatment for diabetes.

Journal Article Am J Physiol Endocrinol Metab · June 2004 Glucagon-like peptide 1 (GLP-1) is a product of proglucagon that is secreted by specialized intestinal endocrine cells after meals. GLP-1 is insulinotropic and plays a role in the incretin effect, the augmented insulin response observed when glucose is abs ... Full text Link to item Cite

Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women.

Conference J Clin Endocrinol Metab · June 2004 Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism. Because fructose, unlike glucose, does not stimulate insulin secretion, we hypothesized that meals high in fructose would result in lower leptin concentrat ... Full text Link to item Cite

Gut peptides in the treatment of diabetes mellitus.

Journal Article Expert Opin Investig Drugs · March 2004 It has been known for at least one century that agents secreted from the intestine during meal absorption regulates glucose assimilation. Extensive research during the past three decades has identified two gut hormones, glucagon-like peptide-1 (GLP-1) and ... Full text Link to item Cite

Effects of glucagon-like peptide 1 on the hepatic glucose metabolism.

Journal Article Horm Metab Res · 2004 Glucagon-like peptide 1 has important actions in lowering blood glucose, both through its incretin action and by regulating other systems affecting glucose metabolism. There is good evidence that the coordinate regulation of islet hormones by GLP-1 has sig ... Full text Link to item Cite

Total pancreatectomy and autologous islet cell transplantation as a means to treat severe chronic pancreatitis.

Conference J Gastrointest Surg · December 2003 Autologous islet cell transplantation after near-total or total pancreatic resection can alleviate pain in patients with severe chronic pancreatitis and preserve endocrine function. From February 2000 to February 2003, a total of 22 patients, whose median ... Full text Link to item Cite

Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes.

Journal Article Horm Metab Res · October 2003 AIMS: To evaluate the safety and efficacy of various doses of recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered subcutaneously (s. c.) via bolus injection or continuous infusion to lower fasting serum glucose (FSG) levels in subjects w ... Full text Link to item Cite

Effect of ingested nutrients on the release of thrittene into the human circulation.

Journal Article J Clin Endocrinol Metab · October 2003 Thrittene is a recently described peptide with a sequence homologous with somatostatin-28 ((1-13)) but is produced independent of the preprosomatostatin gene. It is localized in epithelial cells in stomach and gut mucosal crypts and in neuronal cell bodies ... Full text Link to item Cite

Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect.

Journal Article Am J Physiol Endocrinol Metab · October 2003 Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that stimulates insulin secretion and decreases glucagon release. It has been hypothesized that GLP-1 also reduces glycemia independent of its effect on islet hormones. Based on preliminary evidence ... Full text Link to item Cite

Impaired insulin response after oral but not intravenous glucose in heart- and liver-transplant recipients.

Journal Article Transplantation · September 27, 2003 BACKGROUND: The prevalence of diabetes is high after transplantation. We hypothesized that liver transplantation induces additional alterations of glucose homeostasis because of liver denervation. METHODS: Nondiabetic patients with a heart (n=9) or liver ( ... Full text Link to item Cite

CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors.

Journal Article J Neurosci · July 16, 2003 Responses to stressors serve to adjust physiology and behavior to increase short-term survival at the potential expense of increasing susceptibility to disease over the long term. We show that glucagon-like peptide-1 (7-36) amide (GLP-1) increases levels o ... Full text Link to item Cite

Enteroinsular signaling: perspectives on the role of the gastrointestinal hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in normal and abnormal glucose metabolism.

Journal Article Curr Opin Clin Nutr Metab Care · July 2003 PURPOSE OF REVIEW: The gastrointestinal hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide are emerging as essential regulators of insulin secretion and glucose homeostasis. These peptides, termed incretins, are the key inter ... Full text Link to item Cite

Increased dietary fat attenuates the anorexic effects of intracerebroventricular injections of MTII.

Journal Article Endocrinology · July 2003 The hypothalamic melanocortin (MC) system provides a critical inhibitory control on food intake and body weight. Because access to high-fat (HF) diets is associated with the development of obesity, we hypothesized that increased dietary fat attenuates sign ... Full text Link to item Cite

A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women.

Journal Article J Clin Endocrinol Metab · April 2003 Untested alternative weight loss diets, such as very low carbohydrate diets, have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors. Therefore, we designed a randomized, controlled trial to determine the effects of ... Full text Link to item Cite

Effects of GLP-1-(7-36)NH2, GLP-1-(7-37), and GLP-1- (9-36)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans.

Journal Article J Clin Endocrinol Metab · April 2003 Glucagon-like peptide 1 (GLP-1) is an insulin secretagogue synthesized in the intestine and released in response to meal ingestion. It is secreted primarily in two forms, GLP-1-(7-37) and GLP-1-(7-36)NH(2), both of which bind to a specific GLP-1 receptor ( ... Full text Link to item Cite

A controlled high-fat diet induces an obese syndrome in rats.

Journal Article J Nutr · April 2003 The prevalence of obesity is increasing. Although the etiology of obesity is complex, dietary factors, particularly the consumption of a high-fat (HF) diet, is considered a risk factor for its development. Nonetheless, a causal role of dietary fat has neve ... Full text Link to item Cite

Differential effects of acute and extended infusions of glucagon-like peptide-1 on first- and second-phase insulin secretion in diabetic and nondiabetic humans.

Journal Article Diabetes Care · March 2003 OBJECTIVE: The purpose of this study was to determine whether an extended infusion of the incretin hormone glucagon-like peptide 1 (GLP-1) has a greater effect to promote insulin secretion in type 2 diabetic subjects than acute administration of the peptid ... Full text Link to item Cite

The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness.

Journal Article J Neurosci · December 1, 2002 Intracerebroventricular administration of glucagon-like peptide-1 (7-36) amide (GLP-1) reduces food intake and produces symptoms of visceral illness, such as a conditioned taste aversion (CTA). The central hypothesis of the present work is that separate po ... Full text Link to item Cite

Thrittene, homologous with somatostatin-28((1-13)), is a novel peptide in mammalian gut and circulation.

Journal Article Endocrinology · July 2002 Preprosomatostatin is a gene expressed ubiquitously among vertebrates, and at least two duplications of this gene have occurred during evolution. Somatostatin-28 (S-28) and somatostatin-14 (S-14), C-terminal products of prosomatostatin (ProS), are differen ... Full text Link to item Cite

Impaired beta-cell function, incretin effect, and glucagon suppression in patients with type 1 diabetes who have normal fasting glucose.

Journal Article Diabetes · April 2002 We have recently described a novel phenotype in a group of subjects with type 1 diabetes that is manifested by glucose >11.1 mmol/l 120 min after an oral glucose load, but with normal fasting glucose levels. We now describe the metabolic characteristics of ... Full text Link to item Cite

Cloned mice have an obese phenotype not transmitted to their offspring.

Journal Article Nat Med · March 2002 Mammalian cloning using somatic cells has been accomplished successfully in several species, and its potential basic, clinical and therapeutic applications are being pursued on many fronts. Determining the long-term effects of cloning on offspring is cruci ... Full text Link to item Cite

Inhibition of central amylin signaling increases food intake and body adiposity in rats.

Journal Article Endocrinology · November 2001 Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin by pancreatic beta cells in response to feeding. We recently reported that amylin potently reduces food intake, body weight, and adiposity when delivered into the 3rd cerebral ventr ... Full text Link to item Cite

Activation of the parasympathetic nervous system is necessary for normal meal-induced insulin secretion in rhesus macaques.

Journal Article J Clin Endocrinol Metab · March 2001 Meal-induced insulin secretion is thought to be regulated primarily by absorbed nutrients and incretin hormones released from the gastrointestinal tract. In addition, the parasympathetic nervous system (PNS) is known to mediate preabsorptive, or cephalic p ... Full text Link to item Cite

The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells.

Journal Article Diabetes · September 2000 Islet amyloid polypeptide (IAPP or amylin) is a normal secretory product of the pancreatic beta-cell that is cosecreted with insulin and is the major constituent of islet amyloid deposits in individuals with type 2 diabetes or insulinomas. We have previous ... Full text Link to item Cite

The role of CNS glucagon-like peptide-1 (7-36) amide receptors in mediating the visceral illness effects of lithium chloride.

Journal Article J Neurosci · February 15, 2000 Peripheral administration of large doses of lithium chloride (LiCl) to rats causes a spectrum of effects that are consistent with visceral illness. LiCl reduces food intake, decreases salt ingestion after sodium depletion, induces pica, and produces robust ... Full text Link to item Cite

Glucagon-like peptide 1 (GLP-1) in diabetes and aging

Conference Journal of Anti-Aging Medicine · January 1, 2000 Glucagon-like peptide 1 (GLP-1) is an intestinal hormone that is secreted after meals and augments insulin secretion in response to absorbed glucose. Experiments in animals have demonstrated that GLP-1 is necessary for normal glucose tolerance. GLP-1 is ef ... Full text Cite

Glucose metabolism in elderly patients with type 2 diabetes mellitus

Journal Article Journal of Investigative Medicine · January 1, 1999 Type 2 diabetes mellirus contributes to excess morbidity and mortality among the elderly. Few studies have compared parameters of glucose metabolism in elderly subjects with and without type 2 diabetes. In order to characterize glucose metabolism in the el ... Cite

Abnormal incretin effect in subjects with "silent" type I diabetes

Journal Article Journal of Investigative Medicine · January 1, 1999 PURPOSE:The incretin effect is defined as the augmentation in insulin secretion seen when the glucose is administered orally as compared to intravenously. A group of asymptomatic subjects have been identified through the Diabetes Prevention Trial - Type 1 ... Cite

Severe insulin resistance in a patient with type 1 diabetes and stiff-man syndrome treated with insulin lispro.

Journal Article Diabetes Res Clin Pract · September 1998 We describe a patient with type 1 diabetes with recurrent diabetic ketoacidosis and severe insulin resistance. Extensive evaluation of the etiology of the insulin resistance did not reveal an etiology, and well over 1000 U of daily insulin did not prevent ... Full text Link to item Cite

Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) receptor antagonist attenuates lithium chloride-induced c-Fos induction in rat brainstem.

Journal Article Brain Res · August 10, 1998 Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) and intraperitoneal (i.p.) injection of lithium chloride (LiCl) produce similar patterns of c-Fos induction in the rat brain. These similarities led us to assess the hypothesis that neuronal ... Full text Link to item Cite

Protein, fat, and carbohydrate requirements during starvation: anaplerosis and cataplerosis.

Journal Article Am J Clin Nutr · July 1998 The purpose of this work was to clarify the essentiality of glucose production from amino acids in obese subjects undergoing prolonged starvation and to provide an explanation for death after the depletion of lean body mass when some body fat is still avai ... Full text Link to item Cite

Endogenous somatostatin-28 modulates postprandial insulin secretion. Immunoneutralization studies in baboons.

Journal Article J Clin Invest · November 1, 1997 Somatostatin-28 (S-28), secreted into the circulation from enterocytes after food, and S-14, released mainly from gastric and pancreatic D cells and enteric neurons, inhibit peripheral cellular functions. We hypothesized that S-28 is a humoral regulator of ... Full text Link to item Cite

Transgenic overproduction of islet amyloid polypeptide (amylin) is not sufficient for islet amyloid formation.

Journal Article Horm Metab Res · June 1997 Islet amyloid polypeptide forms islet amyloid deposits in non-insulin-dependent diabetes mellitus. We have generated transgenic mice which express human islet amyloid polypeptide in their pancreatic beta cells yet do not develop islet amyloid deposits desp ... Full text Link to item Cite

Peptide hormone regulation of islet cells.

Journal Article Horm Metab Res · June 1997 Full text Link to item Cite

Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide.

Journal Article Proc Natl Acad Sci U S A · April 16, 1996 Pancreatic islet amyloid deposits are a characteristic pathologic feature of non-insulin-dependent diabetes mellitus and contain islet amyloid polypeptide (IAPP; amylin). We used transgenic mice that express human IAPP in pancreatic beta cells to explore t ... Full text Link to item Cite

Effects of GLP-1 [9-36] NH2, a metabolite of GLP-1 [7-36] NH2, on insulin secretion in Hamster Insulinoma Tumor (HIT) cells

Conference Investigative Ophthalmology and Visual Science · February 15, 1996 GLP-1 [7-36] NH2 (GLP-1) is a potent insulin secretagogue released from the GI tract after meals. GLP-1 is rapidly metabolized to GLP-1 [9-36] NH2 in the circulation, and this truncated form is the predominant GLP-1 species in post-prandial plasma. No biol ... Cite

Elimination of the action of glucagon-like peptide 1 causes an impairment of glucose tolerance after nutrient ingestion by healthy baboons.

Journal Article J Clin Invest · January 1, 1996 Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone released after nutrient ingestion which is known to augment insulin secretion, inhibit glucagon release, and promote insulin-independent glucose disposition. To determine the overall effect of GL ... Full text Link to item Cite

Enteral enhancement of glucose disposition by both insulin-dependent and insulin-independent processes. A physiological role of glucagon-like peptide I.

Journal Article Diabetes · December 1995 Glucagon-like peptide I (GLP-I)(7-36) amide is secreted by intestinal L-cells in response to food ingestion. GLP-I is a potent insulin secretagogue and also inhibits glucagon release. In addition, when given to humans in pharmacological amounts, GLP-I incr ... Full text Link to item Cite

Pancreatic expression and secretion of human islet amyloid polypeptide in a transgenic mouse.

Journal Article Diabetes · December 1994 Islet amyloid polypeptide (IAPP) is a secretory product of the pancreatic beta-cell, which is the primary constituent of the islet amyloid that develops in type II diabetes. To study the role the inherent amyloidogenicity of human IAPP (hIAPP) plays in the ... Full text Link to item Cite

Transgenic mice overproducing islet amyloid polypeptide have increased insulin storage and secretion in vitro.

Journal Article Diabetologia · July 1994 To determine whether chronic overproduction of islet amyloid polypeptide alters beta-cell function, we studied a line of transgenic mice which overexpress islet amyloid polypeptide in their beta-cells. At 3 months of age, these transgenic mice had greater ... Full text Link to item Cite

Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal.

Journal Article J Clin Invest · May 1994 Glucagon-like peptide 1 [7-36 amide] (GLP-1) has been shown to enhance insulin secretion in healthy and type II diabetic humans, and to increase glucose disposal in type I diabetic patients. To further define its action on glucose kinetics, we studied six ... Full text Link to item Cite

Insulin receptor substrate-1 (IRS-1) expression in rat brain.

Journal Article Endocrinology · April 1994 IRS-1 is phosphorylated on tyrosine residues after insulin stimulation and participates in the early events of signal transduction in peripheral insulin-sensitive tissues. This study determined whether neuronal populations in the rat olfactory bulb and hip ... Full text Link to item Cite

Evidence for selective release of rodent islet amyloid polypeptide through the constitutive secretory pathway.

Journal Article Diabetologia · June 1993 To determine the potential for differential release of islet amyloid polypeptide and insulin, we performed studies in rat islet monolayer cultures under conditions known to impair regulated beta-cell secretion. In inhibiting concentrations of epinephrine o ... Full text Link to item Cite

NPY and galanin in a hibernator: hypothalamic gene expression and effects on feeding.

Journal Article Brain Res Bull · 1993 Neuropeptides such as neuropeptide Y (NPY) and galanin may play a role in regulating the pronounced seasonal changes in food intake shown by golden-mantled ground squirrels (Spermophilus saturatus). We used in situ hybridization histochemistry to localize ... Full text Link to item Cite

Response of tGLP-1 to nutrients in humans

Journal Article Digestion · January 1, 1993 Full text Cite

Oxidative and nonoxidative macronutrient disposal in lean and obese men after mixed meals.

Journal Article Am J Clin Nutr · March 1992 Oxidative and nonoxidative macronutrient disposal rates were measured in lean and obese males randomly fed mixed meals containing 0, 33, 67, 100, and 134 kJ/kg fat-free mass (0, 8, 16, 24, and 32 kcal/kg). Body composition, preprandial and postprandial ene ... Full text Link to item Cite

Glucose stimulates and potentiates islet amyloid polypeptide secretion by the B-cell.

Journal Article Horm Metab Res · December 1991 Islet amyloid polypeptide (IAPP) has been shown to be actively secreted by the pancreatic B-cell along with insulin. To determine whether the modulation of B-cell IAPP secretion is similar to that of insulin, we assessed IAPP release in response to glucose ... Full text Link to item Cite

Effect of somatostatin-28 on dynamics of insulin secretion in perfused rat pancreas.

Journal Article Diabetes · September 1991 Somatostatin-28 (S-28), originating in gastrointestinal cells, is secreted into the circulatory system and rises in human plasma after ingestion of a mixed meal. Pancreatic beta-cells contain specific, high-affinity receptors for S-28, and it is plausible ... Full text Link to item Cite

Fasting and postprandial concentrations of somatostatin-28 and somatostatin-14 in type II diabetes in men.

Journal Article Diabetes · October 1990 Recent evidence suggests that somatostatin-28 (SRIF-28), cleaved from prosomatostatin by cells of the upper intestine, acts as a nutrient-stimulated inhibitor of insulin secretion in healthy men. A role for SRIF-28 in the pathophysiology of diabetes has no ... Full text Link to item Cite

Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells.

Journal Article Diabetes · May 1990 Islet amyloid polypeptide (IAPP) has been identified as the major constituent of the pancreatic amyloid of non-insulin-dependent diabetes mellitus (NIDDM) and is also present in normal beta-cell secretory granules. To determine whether IAPP is a pancreatic ... Full text Link to item Cite

Resting metabolic rate and body composition of achondroplastic dwarfs.

Journal Article Medicine (Baltimore) · January 1990 Indirect calorimetry was used to measure resting metabolic rates (RMR), and densitometry and anthropometry were used to measure body fat and fat-free masses of 32 adults with very short stature. Twenty-seven of them were achondroplastic dwarfs. Their resul ... Full text Link to item Cite

Effects of glucagonlike peptide I-(7-36) on release of insulin, glucagon, and somatostatin by rat pancreatic islet cell monolayer cultures.

Journal Article Diabetes · December 1989 Glucagonlike peptide I (GLP-I-(7-36] is cleaved from proglucagon in ileal epithelial cells and increases in human plasma after nutrient ingestion. This peptide has been shown to stimulate insulin secretion in vitro and in vivo and thus potentially acts as ... Full text Link to item Cite

A physiologic role for somatostatin 28 as a regulator of insulin secretion.

Journal Article J Clin Invest · September 1989 Somatostatin 28 (S-28) is a peptide produced in the intestinal tract which rises in the circulation during nutrient absorption. We tested the hypothesis that S-28 regulates B-cell function by (a) studying the effects on insulin secretion of "physiologic" i ... Full text Link to item Cite

Thermic effect of food in lean and obese men.

Journal Article J Clin Invest · June 1988 A systemic reappraisal of the thermic effect of food was done in lean and obese males randomly fed mixed meals containing 0, 8, 16, 24, and 32 kcal/kg fat-free mass. Densitometric analysis was used to measure body composition. Preprandial and postprandial ... Full text Link to item Cite

A reappraisal of the caloric requirements of men.

Journal Article Am J Clin Nutr · December 1987 The resting metabolic rates (RMR) of 60 lean and obese men, aged 18-82 y and weighing 60-171 kg, were measured and body compositions were determined. Body compositional variables reflecting active protoplasmic tissue were all highly interrelated. Body weig ... Full text Link to item Cite