Scholars@Duke
Jonathan Edward Campbell

Jonathan Edward Campbell

Associate Professor in Medicine
Medicine, Endocrinology, Metabolism, and Nutrition

Selected Publications

Acute exogenous acyl-GIP treatment enhances lipid handling and fatty acid oxidation by involving brown fat.

Journal Article EMBO Rep · November 2025 The contribution of glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling in brown adipose tissue (BAT) remains underexplored. We studied the acute effects of exogenous acyl-GIP (1 nmol/kg) administration on whole-body lipid handling and ... Full text Link to item Cite

α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.

Journal Article Sci Adv · September 19, 2025 α cells secrete proglucagon peptides to regulate nutrient metabolism. Recent findings support an α cell-to-β cell axis that is mediated by paracrine signaling through the glucagon receptor and glucagon-like peptide 1 (GLP-1) receptor in β cells. To address ... Full text Link to item Cite

β Cell Gαs signaling is critical for physiological and pharmacological enhancement of insulin secretion.

Journal Article J Clin Invest · August 15, 2025 The incretin peptides glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors coordinate β cell secretion that is proportional to nutrient intake. This effect permits consistent and restricted glucose excursions across a range of ... Full text Link to item Cite

Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication.

Journal Article Cell Metab · August 5, 2025 Pancreatic alpha cells modulate beta cell function in a paracrine manner through the release of glucagon. However, the detailed molecular architecture underlying alpha-to-beta cell regulation remains poorly characterized. Here, we show that the glucagon-li ... Full text Link to item Cite

Therapeutic Targeting of the GIP Receptor-Revisiting the Controversies.

Journal Article Diabetes · August 1, 2025 Current and emerging strategies to therapeutically target weight management include pairing agonism of the glucagon-like peptide 1 receptor (GLP-1R) with either agonism or antagonism of the glucose-dependent insulinotropic polypeptide receptor (GIPR). On t ... Full text Link to item Cite

Islet hormones at the intersection of glucose and amino acid metabolism.

Journal Article Nat Rev Endocrinol · July 2025 The pancreatic islets of Langerhans are central to fine-tuning metabolism to ensure metabolic homeostasis during the transition between fasting and feeding. Insulin and glucagon, the principal hormones generated and secreted by islets, exert powerful contr ... Full text Link to item Cite

Development of a succinyl CoA:3-ketoacid CoA transferase inhibitor selective for peripheral tissues that improves glycemia in obesity

Journal Article Iscience · May 16, 2025 Many individuals with type 2 diabetes (T2D) cannot take current therapies due to their adverse effects. Thus, new glucose-lowering agents targeting unique mechanisms are needed. Studies have demonstrated that decreasing ketone oxidation, secondary to muscl ... Full text Cite

Glucose-dependent insulinotropic polypeptide (GIP).

Journal Article Mol Metab · May 2025 BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in the maintenance of glucose tolerance in healthy humans. Until recently GIP had not been developed as a therapeutic and thus has ... Full text Link to item Cite

Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits.

Journal Article J Clin Invest · October 22, 2024 Following a meal, glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), the 2 major incretins promoting insulin release, are secreted from specialized enteroendocrine cells (L and K cells, respectively). Although GIP is the ... Full text Link to item Cite

Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes.

Journal Article Nat Metab · July 2024 Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes1. Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) rece ... Full text Link to item Cite

Evaluating glucose-dependent insulinotropic polypeptide and glucagon as key regulators of insulin secretion in the pancreatic islet.

Journal Article Am J Physiol Endocrinol Metab · July 1, 2024 The incretin axis is an essential component of postprandial insulin secretion and glucose homeostasis. There are two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which exert multiple actions thr ... Full text Link to item Cite

Intra-islet α-cell Gs signaling promotes glucagon release.

Journal Article Nat Commun · June 15, 2024 Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell s ... Full text Link to item Cite

GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells.

Journal Article Peptides · May 2024 Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are transmembrane receptors involved in insulin, glucagon and somatostatin secretion from the pancreatic islet. Therapeutic targeting of GLP1R and GIP ... 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

Glucagon in Islet and Metabolic Regulation

Chapter · January 1, 2024 This chapter reviews basic concepts in alpha-cell biology and glucagon physiology with an emphasis on how the processes are altered in disease states, particularly diabetes. It discusses relatively new findings that implicate glucagon in intra-islet signal ... Full text 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

GPCR Promiscuity Reshapes Islet Physiology.

Journal Article Diabetes · September 1, 2023 The family of proglucagon peptides Includes glucagon and glucagon-like peptide 1 (GLP-1), two unique peptides derived from the same prohormone. Despite numerous similarities between the peptides, these have long been viewed as having opposing actions on me ... Full text Link to item Cite

100 years of glucagon and 100 more.

Journal Article Diabetologia · August 2023 The peptide hormone glucagon, discovered in late 1922, is secreted from pancreatic alpha cells and is an essential regulator of metabolic homeostasis. This review summarises experiences since the discovery of glucagon regarding basic and clinical aspects o ... Full text Link to item Cite

Fibroblast growth factor-21 is required for weight loss induced by the glucagon-like peptide-1 receptor agonist liraglutide in male mice fed high carbohydrate diets.

Journal Article Mol Metab · June 2023 OBJECTIVE: Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RA) and fibroblast growth factor-21 (FGF21) confer similar metabolic benefits. GLP-1RA induce FGF21, leading us to investigate mechanisms engaged by the GLP-1RA liraglutide to increase FGF ... 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

Hypothalamic and brainstem glucose-dependent insulinotropic polypeptide receptor neurons employ distinct mechanisms to affect feeding.

Journal Article JCI Insight · May 22, 2023 Central glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) signaling is critical in GIP-based therapeutics' ability to lower body weight, but pathways leveraged by GIPR pharmacology in the brain remain incompletely understood. We explored t ... Full text Link to item Cite

Pancreas-derived DPP4 is not essential for glucose homeostasis under metabolic stress.

Journal Article iScience · May 19, 2023 Mice systemically lacking dipeptidyl peptidase-4 (DPP4) have improved islet health, glucoregulation, and reduced obesity with high-fat diet (HFD) feeding compared to wild-type mice. Some, but not all, of this improvement can be linked to the loss of DPP4 i ... 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

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

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

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

Journal Article Cell Metab · November 1, 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 Link to item Cite

GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice.

Journal Article Nat Metab · August 2022 Dual agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPARɑ/ɣ) have beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to potential adverse eff ... Full text Link to item Cite

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

Journal Article Diabetes · May 1, 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 Link to item Cite

Ildr1 gene deletion protects against diet-induced obesity and hyperglycemia.

Journal Article PLoS One · 2022 OBJECTIVE: Immunoglobulin-like Domain-Containing Receptor 1 (ILDR1) is expressed on nutrient sensing cholecystokinin-positive enteroendocrine cells of the gastrointestinal tract and it has the unique ability to induce fat-mediated CCK secretion. However, t ... Full text Link to item Cite

Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion.

Journal Article Cell Metab · April 6, 2021 Metabolic fuels regulate insulin secretion by generating second messengers that drive insulin granule exocytosis, but the biochemical pathways involved are incompletely understood. Here we demonstrate that stimulation of rat insulinoma cells or primary rat ... Full text Link to item Cite

Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms.

Journal Article Mol Metab · April 2021 BACKGROUND: Glucose-dependent insulinotropic peptide (GIP) is one of two incretin hormones that communicate nutrient intake with systemic metabolism. Although GIP was the first incretin hormone to be discovered, the understanding of GIP's biology was quick ... Full text Link to item Cite

Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation.

Journal Article Endocr Rev · March 15, 2021 Glucagon-like peptide-1 (GLP-1) is produced in gut endocrine cells and in the brain, and acts through hormonal and neural pathways to regulate islet function, satiety, and gut motility, supporting development of GLP-1 receptor (GLP-1R) agonists for the tre ... Full text Link to item 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

Mechanisms controlling pancreatic islet cell function in insulin secretion.

Journal Article Nat Rev Mol Cell Biol · February 2021 Metabolic homeostasis in mammals is tightly regulated by the complementary actions of insulin and glucagon. The secretion of these hormones from pancreatic β-cells and α-cells, respectively, is controlled by metabolic, endocrine, and paracrine regulatory m ... 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 AbstractMany 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' h ... Full text Cite

Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway.

Journal Article Cell Metab · November 3, 2020 Pancreatic β cells couple nutrient metabolism with appropriate insulin secretion. Here, we show that pyruvate kinase (PK), which converts ADP and phosphoenolpyruvate (PEP) into ATP and pyruvate, underlies β cell sensing of both glycolytic and mitochondrial ... Full text Link to item Cite

Repositioning the Alpha Cell in Postprandial Metabolism.

Journal Article Endocrinology · November 1, 2020 Glucose homeostasis is maintained in large part due to the actions of the pancreatic islet hormones insulin and glucagon, secreted from β- and α-cells, respectively. The historical narrative positions these hormones in opposition, with insulin primarily re ... Full text Link to item Cite

β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2020 Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in ... Full text Link to item 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

Pimozide Alleviates Hyperglycemia in Diet-Induced Obesity by Inhibiting Skeletal Muscle Ketone Oxidation.

Journal Article Cell Metab · May 5, 2020 Perturbations in carbohydrate, lipid, and protein metabolism contribute to obesity-induced type 2 diabetes (T2D), though whether alterations in ketone body metabolism influence T2D pathology is unknown. We report here that activity of the rate-limiting enz ... 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

Repositioning Glucagon Action in the Physiology and Pharmacology of Diabetes.

Journal Article Diabetes · April 2020 Glucagon is historically described as the counterregulatory hormone to insulin, induced by fasting/hypoglycemia to raise blood glucose through action mediated in the liver. However, it is becoming clear that the biology of glucagon is much more complex and ... Full text Link to item Cite

The role of GIP in α-cells and glucagon secretion.

Journal Article Peptides · March 2020 Glucose-dependent insulinotropic polypeptide (GIP) is an intestinally derived peptide that is secreted in response to feeding. The GIP receptor (GIPR) is expressed in many cell types involved in the regulation of metabolism, including α- and β-cells. Gluca ... 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

l-Citrulline supplementation improves glucose and exercise tolerance in obese male mice.

Journal Article Exp Physiol · February 2020 What is the central question of the study? Does the action of l-citrulline, which has been shown to augment performance in animals and athletes, possibly via increasing mitochondrial function, translate to obese animals, and does this improve glycaemia? Wh ... 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

Physiological roles of the GIP receptor in murine brown adipose tissue.

Journal Article Mol Metab · October 2019 OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistan ... 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

Reg3 Proteins as Gut Hormones? Don't Be Hasty.

Journal Article Endocrinology · July 1, 2019 Full text Link to item Cite

The brown adipose tissue glucagon receptor is functional but not essential for control of energy homeostasis in mice.

Journal Article Mol Metab · April 2019 OBJECTIVE: Administration of glucagon (GCG) or GCG-containing co-agonists reduces body weight and increases energy expenditure. These actions appear to be transduced by multiple direct and indirect GCG receptor (GCGR)-dependent mechanisms. Although the can ... Full text Link to item 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

Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition.

Journal Article Cell Metab · February 5, 2019 Dipeptidyl peptidase-4 (DPP-4) controls glucose homeostasis through enzymatic termination of incretin action. We report that plasma DPP-4 activity correlates with body weight and fat mass, but not glucose control, in mice. Genetic disruption of adipocyte D ... Full text Link to item Cite

Targeting the Incretin/Glucagon System With Triagonists to Treat Diabetes.

Journal Article Endocr Rev · October 1, 2018 Glucagonlike peptide 1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of glucagonlike peptide 1 receptor-directed strategies is s ... 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

Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin promoter, improves glucose tolerance in mice fed a high-fat diet.

Journal Article Diabetologia · August 2018 AIMS/HYPOTHESIS: Cre-loxP systems are frequently used in mouse genetics as research tools for studying tissue-specific functions of numerous genes/proteins. However, the expression of Cre recombinase in a tissue-specific manner often produces undesirable c ... Full text Link to item Cite

Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition.

Journal Article Cell Rep · July 3, 2018 SIRT3 is a nicotinamide adenine dinucleotide (NAD+)-dependent mitochondrial protein deacetylase purported to influence metabolism through post-translational modification of metabolic enzymes. Fuel-stimulated insulin secretion, which involves mitochondrial ... Full text Link to item Cite

Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction.

Journal Article Cell Metab · February 6, 2018 Incretin hormones exert pleiotropic metabolic actions beyond the pancreas. Although the heart expresses both incretin receptors, the cardiac biology of GIP receptor (GIPR) action remains incompletely understood. Here we show that GIPR agonism did not impai ... Full text Link to item Cite

β-Cell Inactivation of Gpr119 Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation.

Journal Article Diabetes · June 2017 GPR119 was originally identified as an orphan β-cell receptor; however, subsequent studies demonstrated that GPR119 also regulates β-cell function indirectly through incretin hormone secretion. We assessed the importance of GPR119 for β-cell function in Gp ... Full text Link to item Cite

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion.

Journal Article Cell Metab · April 4, 2017 Sirtuins are NAD+-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control h ... 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

Cellular Sites and Mechanisms Linking Reduction of Dipeptidyl Peptidase-4 Activity to Control of Incretin Hormone Action and Glucose Homeostasis.

Journal Article Cell Metab · January 10, 2017 Pharmacological inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme potentiates incretin action and is widely used to treat type 2 diabetes. Nevertheless, the precise cells and tissues critical for incretin degradation and glucose homeostasis remain unk ... Full text Link to item Cite

Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat-Fed Diabetic Mice.

Journal Article Diabetes · March 2016 Dipeptidyl peptidase-4 (DPP4) inhibitors used for the treatment of type 2 diabetes are cardioprotective in preclinical studies; however, some cardiovascular outcome studies revealed increased hospitalization rates for heart failure (HF) among a subset of D ... Full text Link to item Cite

TCF1 links GIPR signaling to the control of beta cell function and survival.

Journal Article Nat Med · January 2016 The glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor transduce nutrient-stimulated signals to control beta cell function. Although the GLP-1 receptor (GLP-1R) is a validated drug target for diabet ... Full text Link to item Cite

Incretin-based therapies for the failing heart

Journal Article Cardiovascular Endocrinology · January 1, 2016 The gut incretin hormone, glucagon-like peptide 1 (GLP-1), regulates islet hormone secretion, circulating glucose levels, and body weight, making it an attractive agent for the treatment of type 2 diabetes. As cardiovascular disease represents the leading ... Full text Cite

Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone.

Journal Article Diabetes · November 2015 There is growing concern over confounding artifacts associated with β-cell-specific Cre-recombinase transgenic models, raising questions about their general usefulness in research. The inducible β-cell-specific transgenic (MIP-CreERT(1Lphi)) mouse was desi ... Full text Link to item Cite

Islet α cells and glucagon--critical regulators of energy homeostasis.

Journal Article Nat Rev Endocrinol · June 2015 Glucagon is secreted from islet α cells and controls blood levels of glucose in the fasting state. Impaired glucagon secretion predisposes some patients with type 1 diabetes mellitus (T1DM) to hypoglycaemia; whereas hyperglycaemia in patients with T1DM or ... Full text Link to item Cite

Glucagon-like peptide-1 receptor agonists increase pancreatic mass by induction of protein synthesis.

Journal Article Diabetes · March 2015 Glucagon-like peptide-1 (GLP-1) controls glucose homeostasis by regulating secretion of insulin and glucagon through a single GLP-1 receptor (GLP-1R). GLP-1R agonists also increase pancreatic weight in some preclinical studies through poorly understood mec ... Full text Link to item Cite

A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents.

Journal Article Nat Med · January 2015 We report the discovery of a new monomeric peptide that reduces body weight and diabetic complications in rodent models of obesity by acting as an agonist at three key metabolically-related peptide hormone receptors: glucagon-like peptide-1 (GLP-1), glucos ... Full text Link to item Cite

Inactivation of the cardiomyocyte glucagon-like peptide-1 receptor (GLP-1R) unmasks cardiomyocyte-independent GLP-1R-mediated cardioprotection.

Journal Article Mol Metab · August 2014 GLP-1R agonists improve outcomes in ischemic heart disease. Here we studied GLP-1R-dependent adaptive and cardioprotective responses to ventricular injury. Glp1r (-/-) hearts exhibited chamber-specific differences in gene expression, but normal mortality a ... Full text Link to item Cite

Pharmacology, physiology, and mechanisms of incretin hormone action.

Journal Article Cell Metab · June 4, 2013 Incretin peptides, principally GLP-1 and GIP, regulate islet hormone secretion, glucose concentrations, lipid metabolism, gut motility, appetite and body weight, and immune function, providing a scientific basis for utilizing incretin-based therapies in th ... Full text Link to item Cite

GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE(-/-) mice.

Journal Article Endocrinology · January 2013 Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce lipid accumulation in peripheral tissues, attenuating atherosclerosis and hepatic steatosis in preclinical studies. We examined whether GLP-1R activation decreases atherosclerosis progression in hig ... Full text Link to item Cite

A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat feeding.

Journal Article Dis Model Mech · September 2012 Glucocorticoids (GCs) are potent pharmacological agents used to treat a number of immune conditions. GCs are also naturally occurring steroid hormones (e.g. cortisol, corticosterone) produced in response to stressful conditions that are thought to increase ... Full text Link to item Cite

Gipr is essential for adrenocortical steroidogenesis; however, corticosterone deficiency does not mediate the favorable metabolic phenotype of Gipr(-/-) mice.

Journal Article Diabetes · January 2012 Glucose-dependent insulinotropic polypeptide (GIP) promotes glucose-dependent insulin secretion. However, GIP also enhances glucocorticoid secretion and promotes adiposity. Because obesity and diabetes are glucocorticoid dependent, we examined whether the ... Full text Link to item Cite

Skeletal muscle protein synthesis and the abundance of the mRNA translation initiation repressor PDCD4 are inversely regulated by fasting and refeeding in rats.

Journal Article Am J Physiol Endocrinol Metab · June 2011 Optimal skeletal muscle mass is vital to human health, because defects in muscle protein metabolism underlie or exacerbate human diseases. The mammalian target of rapamycin complex 1 is critical in the regulation of mRNA translation and protein synthesis. ... Full text Link to item Cite

Anti-lipolytic effects of glucocorticoids

Conference FASEB JOURNAL · April 1, 2011 Link to item Cite

Adipogenic and lipolytic effects of chronic glucocorticoid exposure.

Journal Article Am J Physiol Cell Physiol · January 2011 Glucocorticoids have been proposed to be both adipogenic and lipolytic in action within adipose tissue, although it is unknown whether these actions can occur simultaneously. Here we investigate both the in vitro and in vivo effects of corticosterone (Cort ... Full text Link to item Cite

Impaired growth and force production in skeletal muscles of young partially pancreatectomized rats: a model of adolescent type 1 diabetic myopathy?

Journal Article PLoS One · November 17, 2010 This present study investigated the temporal effects of type 1 diabetes mellitus (T1DM) on adolescent skeletal muscle growth, morphology and contractile properties using a 90% partial pancreatecomy (Px) model of the disease. Four week-old male Sprague-Dawl ... Full text Link to item Cite

Regular exercise prevents the development of hyperglucocorticoidemia via adaptations in the brain and adrenal glands in male Zucker diabetic fatty rats.

Journal Article Am J Physiol Regul Integr Comp Physiol · July 2010 We determined the effects of voluntary wheel running on the hypothalamic-pituitary-adrenal (HPA) axis, and the peripheral determinants of glucocorticoids action, in male Zucker diabetic fatty (ZDF) rats. Six-week-old euglycemic ZDF rats were divided into B ... Full text Link to item Cite

Exercise maintains euglycemia in association with decreased activation of c-Jun NH2-terminal kinase and serine phosphorylation of IRS-1 in the liver of ZDF rats.

Journal Article Am J Physiol Endocrinol Metab · March 2010 Stress-activated systems and oxidative stress are involved in insulin resistance, which, along with beta-cell failure, contribute to the development of type 2 diabetes mellitus (T2DM). Exercise improves insulin resistance and glucose tolerance, and these a ... Full text Link to item Cite

Endurance exercise training increases adipose tissue glucocorticoid exposure: adaptations that facilitate lipolysis.

Journal Article Metabolism · May 2009 Glucocorticoids (GCs) have long been thought to be lipolytic in nature. Recently, however, increased exposure to GCs in insulin-sensitive tissues has been associated with lipid accumulation and metabolic complications, regardless of plasma concentrations. ... Full text Link to item Cite

Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training.

Journal Article J Appl Physiol (1985) · January 2009 Although exercise is a common and potent activator of the hypothalamic-pituitary adrenal (HPA) axis, the effects of exercise on the acute stress response are not well understood. Here, we investigated the effects of short- (2 wk) and long-term (8 wk) volun ... Full text Link to item Cite

Streptozotocin induces G2 arrest in skeletal muscle myoblasts and impairs muscle growth in vivo.

Journal Article Am J Physiol Cell Physiol · March 2007 Streptozotocin (STZ) is used extensively to induce pancreatic beta-cell death and ultimately diabetes mellitus in animal models. However, the direct effects of STZ on muscle are largely unknown. To delineate the effects of STZ from the effects of hypoinsul ... Full text Link to item Cite

Efficacy of continuous real-time blood glucose monitoring during and after prolonged high-intensity cycling exercise: spinning with a continuous glucose monitoring system.

Journal Article Diabetes Technol Ther · December 2006 BACKGROUND: Hypoglycemia is the most common and serious side effect of insulin therapy in type 1 diabetes (T1DM), frequently occurring both during and after vigorous exercise. Late-onset hypoglycemia (LOH) is of great concern, occurring 1-36 h after exerci ... Full text Link to item Cite

Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats.

Journal Article J Appl Physiol (1985) · June 2006 Adaptations of the hypothalamic-pituitary-adrenal (HPA) axis to voluntary exercise in rodents are not clear, because most investigations use forced-exercise protocols, which are associated with psychological stress. In the present study, we examined the ef ... Full text Link to item Cite

Effect of voluntary exercise on peripheral tissue glucocorticoid receptor content and the expression and activity of 11beta-HSD1 in the Syrian hamster.

Journal Article J Appl Physiol (1985) · May 2006 Recent findings indicate that elevated levels of glucocorticoids (GC), governed by the expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and GC receptors (GR), in visceral adipose tissue and skeletal muscle lead to increased insulin re ... Full text Link to item Cite

Metabolic effects of voluntary wheel running in young and old Syrian golden hamsters.

Journal Article Physiol Behav · February 28, 2006 To explore the metabolic effects of high volume wheel running in the Syrian golden hamster, 6-week old (YOUNG) and 6-month old (OLD) male animals were randomly divided into sedentary (i.e., YOUNG-S or OLD-S) or running wheel (i.e., YOUNG-RW or OLD-RW) grou ... Full text Link to item Cite

IL-10 induces regulatory T cell apoptosis by up-regulation of the membrane form of TNF-alpha.

Journal Article J Immunol · January 15, 2004 Numerous studies have demonstrated the role of regulatory T (Treg) cells in peripheral tolerance. Nevertheless, how the survival and death of Treg cells is controlled is largely unknown. In this study, we investigated the mechanisms involved in regulating ... Full text Link to item Cite