Scholars@Duke
Derek Nunez

Derek Nunez

Adjunct Professor in the Department of Medicine
Medicine, Endocrinology, Metabolism, and Nutrition

Scholarly Works - Journal articles

Clobetasol Propionate Ophthalmic Suspension to Treat Ocular Inflammation and Pain after Uncomplicated Cataract Surgery.

Journal article Ophthalmology · August 2026 PURPOSE: To evaluate the efficacy and safety of clobetasol propionate ophthalmic suspension (CPN) 0.05% to treat ocular inflammation and pain after cataract surgery. DESIGN: Two multicenter, randomized, double-masked, placebo-controlled phase 3 trials, ide ... Full text Link to item Cite

Dose-selection study of clobetasol propionate ophthalmic suspension that evaluated inflammation and pain after cataract surgery.

Journal article J Cataract Refract Surg · May 1, 2026 PURPOSE: To evaluate clobetasol propionate ophthalmic suspension (CPN) as treatment for inflammation and pain after cataract surgery. SETTING: 9 outpatient surgery centers in the United States. DESIGN: Randomized, double-masked, placebo-controlled, dose-se ... 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

Factors influencing longitudinal changes of circulating liver enzyme concentrations in subjects randomized to placebo in four clinical trials.

Journal article Am J Physiol Gastrointest Liver Physiol · March 1, 2019 Liver enzyme concentrations are measured as safety end points in clinical trials to detect drug-related hepatotoxicity, but little is known about the epidemiology of these biomarkers in subjects without hepatic dysfunction who are enrolled in drug trials. ... Full text Open Access Link to item Cite

Assessment of plasma acylcarnitines before and after weight loss in obese subjects.

Journal article Arch Biochem Biophys · September 15, 2016 Acylcarnitines, fatty acid oxidation (FAO) intermediates, have been implicated in diet-induced insulin resistance and type 2 diabetes mellitus, as increased levels are found in obese insulin resistant humans. Moreover plasma acylcarnitines have been associ ... Full text Link to item Cite

Glucose and lipid effects of the ileal apical sodium-dependent bile acid transporter inhibitor GSK2330672: double-blind randomized trials with type 2 diabetes subjects taking metformin.

Journal article Diabetes Obes Metab · July 2016 AIMS: To investigate the pharmacodynamics, pharmacokinetics and safety/tolerability of blocking reuptake of bile acids using the inhibitor GSK2330672 (GSK672) in patients with type 2 diabetes (T2D). METHODS: Subjects with T2D taking metformin were enrolled ... Full text Link to item Cite

Therapeutic potential of Takeda-G-protein-receptor-5 (TGR5) agonists. Hope or hype?

Journal article Diabetes Obes Metab · May 2016 The gastrointestinal tract regulates glucose and energy metabolism, and there is increasing recognition that bile acids function as key signalling molecules in these processes. For example, bile acid changes that occur after bariatric surgery have been imp ... Full text Link to item Cite

A Systematic Review of Biomarkers and Risk of Incident Type 2 Diabetes: An Overview of Epidemiological, Prediction and Aetiological Research Literature.

Journal article PLoS One · 2016 BACKGROUND: Blood-based or urinary biomarkers may play a role in quantifying the future risk of type 2 diabetes (T2D) and in understanding possible aetiological pathways to disease. However, no systematic review has been conducted that has identified and p ... Full text Link to item Cite

Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes.

Journal article PLoS One · 2016 BACKGROUND: Nutritional agents have modest efficacy in reducing weight and blood glucose in animal models and humans, but combinations are less well characterized. GSK2890457 (GSK457) is a combination of 4 nutritional agents, discovered by the systematic a ... Full text Link to item Cite

GSK2374697, a long duration glucagon-like peptide-1 (GLP-1) receptor agonist, reduces postprandial circulating endogenous total GLP-1 and peptide YY in healthy subjects.

Journal article Diabetes Obes Metab · October 2015 We investigated the effects of a long-duration glucagon-like peptide-1 (GLP-1) receptor agonist, GSK2374697, on postprandial endogenous total GLP-1 and peptide YY (PYY). Two cohorts of healthy subjects, one normal/overweight and one obese, were randomized ... Full text Link to item Cite

Pharmacokinetics and Tolerability of Exenatide Delivered by 7-Day Continuous Subcutaneous Infusion in Healthy Volunteers.

Journal article Adv Ther · July 2015 INTRODUCTION: Small peptides are approved as treatments for type 2 diabetes mellitus and may have utility in metabolic diseases. These peptides often have short half-lives requiring delivery either as a sustained-release formulation or via a device. The op ... Full text Link to item Cite

GSK2374697, a novel albumin-binding domain antibody (AlbudAb), extends systemic exposure of exendin-4: first study in humans--PK/PD and safety.

Journal article Clin Pharmacol Ther · December 2014 GSK2374697 is a genetically engineered fusion protein of a human domain antibody to exendin-4. This molecule binds with a high affinity to human serum albumin, creating a long-duration glucagon-like peptide-1 (GLP-1) receptor agonist. This study is the fir ... Full text Link to item Cite

Effect of two dietary fibers on satiety and glycemic parameters: a randomized, double-blind, placebo-controlled, exploratory study.

Journal article Nutr J · May 17, 2014 BACKGROUND: Dietary carbohydrates may affect metabolic and physiologic parameters. The present study evaluated whether a combination of two dietary fibers, oligofructose (OFS) and pectin (P), altered satiety and glycemic parameters. The primary objective o ... Full text Link to item Cite

Exploring glycosuria as a mechanism for weight and fat mass reduction. A pilot study with remogliflozin etabonate and sergliflozin etabonate in healthy obese subjects.

Journal article J Clin Transl Endocrinol · March 2014 Inhibitors of sodium-dependent glucose co-transporter 2 (SGLT2) increase glucose excretion in the urine and improve blood glucose in Type 2 diabetes mellitus. Glycosuria provides an energy and osmotic drain that could alter body composition. We therefore c ... Full text Link to item Cite

Gut hormone pharmacology of a novel GPR119 agonist (GSK1292263), metformin, and sitagliptin in type 2 diabetes mellitus: results from two randomized studies.

Journal article PLoS One · 2014 UNLABELLED: GPR119 receptor agonists improve glucose metabolism and alter gut hormone profiles in animal models and healthy subjects. We therefore investigated the pharmacology of GSK1292263 (GSK263), a selective GPR119 agonist, in two randomized, placebo- ... Full text Link to item Cite

Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus.

Journal article PLoS One · 2014 UNLABELLED: Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects ... Full text Link to item Cite

Safety, Pharmacokinetics, and Pharmacodynamic Effects of a Selective TGR5 Agonist, SB-756050, in Type 2 Diabetes.

Journal article Clin Pharmacol Drug Dev · July 2013 TGR5 is a bile acid receptor and a potential target for the treatment of type 2 diabetes (T2D). We report here the safety, pharmacokinetics, and pharmacodynamic effects of a selective TGR5 agonist, SB-756050, in patients with T2D. Fifty-one subjects were r ... Full text Link to item Cite

Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clinical study design.

Journal article Xenobiotica · June 2013 1. This work investigated the drug interaction potential of GSK1292263, a novel GPR119 agonist, with the HMG-coA reductase inhibitors simvastatin and rosuvastatin. 2. In vitro experiments assessed the inhibition of transporters and CYP enzymes by GSK129226 ... Full text Link to item Cite

First human dose-escalation study with remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type 2 diabetes mellitus.

Journal article BMC Pharmacol Toxicol · May 13, 2013 BACKGROUND: Remogliflozin etabonate (RE) is the prodrug of remogliflozin, a selective inhibitor of the renal sodium-dependent glucose transporter 2 (SGLT2), which could increase urine glucose excretion (UGE) and lower plasma glucose in humans. METHODS: Thi ... Full text Link to item Cite

Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2, improves serum glucose profiles in type 1 diabetes.

Journal article Diabetes Care · November 2012 OBJECTIVE: Remogliflozin etabonate (RE), an inhibitor of the sodium-glucose transporter 2, improves glucose profiles in type 2 diabetes. This study assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of RE in subjects with type 1 diabetes ... Full text Link to item Cite

Prediction of weight loss and regain following dietary, lifestyle, and pharmacologic intervention.

Journal article Clin Pharmacol Ther · June 2012 To develop statistical models for predicting weight loss and regain, we analyzed the phenotypic responses in an outpatient study of 60 obese subjects randomized to one of three 12-week interventions, diet (-600 kcal) alone, diet with exercise, and diet wit ... Full text Link to item Cite

Reduced T2* values in soleus muscle of patients with type 2 diabetes mellitus.

Journal article PLoS One · 2012 Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affect ... Full text Link to item Cite

Assessment of acute and chronic pharmacological effects on energy expenditure and macronutrient oxidation in humans: responses to ephedrine.

Journal article J Obes · 2011 Evidence of active brown adipose tissue in human adults suggests that this may become a pharmacological target to induce negative energy balance. We have explored whole-body indirect calorimetry to detect the metabolic effects of thermogenic drugs through ... Full text Link to item Cite

Multiple-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy overweight and obese subjects: a randomized double-blind study.

Journal article J Clin Pharmacol · June 2010 Sergliflozin, the active entity of sergliflozin etabonate, is a selective inhibitor of the sodium-dependent glucose cotransporter-2 in the renal tubule. The pharmacokinetics and pharmacodynamics of sergliflozin were examined during administration of sergli ... Full text Link to item Cite

Single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a novel inhibitor of glucose reabsorption, in healthy volunteers and patients with type 2 diabetes mellitus.

Journal article J Clin Pharmacol · June 2010 Sergliflozin, the active entity of sergliflozin etabonate, is a selective inhibitor of sodium-dependent glucose cotransporter 2 (SGLT2). The pharmacokinetics and pharmacodynamics of sergliflozin were evaluated following single oral dose administration of s ... Full text Link to item Cite

The Biomarkers Consortium: practice and pitfalls of open-source precompetitive collaboration.

Journal article Clin Pharmacol Ther · May 2010 Precompetitive collaboration is a growing driver for innovation and increased productivity in biomedical science and drug development. The Biomarkers Consortium, a public-private platform for precompetitive collaboration specific to biomarkers, demonstrate ... Full text Link to item Cite

Quantitative magnetic resonance (QMR) for longitudinal evaluation of body composition changes with two dietary regimens.

Journal article Obesity (Silver Spring) · February 2010 We have recently reported a validation study of a prototype low-field strength quantitative magnetic resonance (QMR) instrument for measurement of human body composition (EchoMRI-AH). QMR was very precise, but underreported fat mass (FM) by 2-4 kg when com ... Full text Link to item Cite

Utility of adiponectin as a biomarker predictive of glycemic efficacy is demonstrated by collaborative pooling of data from clinical trials conducted by multiple sponsors.

Journal article Clin Pharmacol Ther · December 2009 This study, conducted under the Metabolic Disorders Steering Committee of the Biomarkers Consortium (a public-private partnership managed by the Foundation for the National Institutes of Health (FNIH)), analyzed blinded data on 2,688 type 2 diabetes (T2D) ... Full text Link to item Cite

MRI assessment of drug-induced fluid accumulation in humans: validation of the technology.

Journal article Magn Reson Imaging · June 2008 PURPOSE: The purpose of this study was to evaluate the feasibility of using proton and sodium magnetic resonance imaging (MRI) to detect fluid accumulation produced by fludrocortisone and nifedipine - two drugs known to cause salt/water retention by differ ... Full text Link to item Cite

Validation of a quantitative magnetic resonance method for measuring human body composition.

Journal article Obesity (Silver Spring) · January 2008 OBJECTIVE: To evaluate a novel quantitative magnetic resonance (QMR) methodology (EchoMRI-AH, Echo Medical Systems) for measurement of whole-body fat and lean mass in humans. METHODS AND PROCEDURES: We have studied (i) the in vitro accuracy and precision b ... Full text Link to item Cite

A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human.

Journal article Physiol Genomics · April 24, 2007 Type 2 diabetes mellitus is the result of a combination of impaired insulin secretion with reduced insulin sensitivity of target tissues. There are an estimated 150 million affected individuals worldwide, of whom a large proportion remains undiagnosed beca ... Full text Link to item Cite

Proton and sodium MRI assessment of fluid level in calf tissue.

Journal article J Magn Reson Imaging · July 2006 PURPOSE: To investigate the feasibility of using (1)H and (23)Na MRI to detect fluid levels in the lower leg muscle. MATERIALS AND METHODS: Proton and sodium MRI was applied to detect body fluid levels in the lower leg muscles of 18 healthy young male subj ... Full text Link to item Cite

alpha-Tropomyosin mutations Asp(175)Asn and Glu(180)Gly affect cardiac function in transgenic rats in different ways.

Journal article Am J Physiol Regul Integr Comp Physiol · September 2004 To study the mechanisms by which missense mutations in alpha-tropomyosin cause familial hypertrophic cardiomyopathy, we generated transgenic rats overexpressing alpha-tropomyosin with one of two disease-causing mutations, Asp(175)Asn or Glu(180)Gly, and an ... Full text Link to item Cite

Regional hemodynamic effects of the N-(2-benzoylphenyl)-L-tyrosine peroxisome proliferator-activated receptor-gamma ligand, GI 262570 [(S)-2-(2-benzoylphenylamino)-3-[4-[2-(5-methyl-2-phenyl-2-oxazol-4-yl)ethoxy]phenyl]propionic acid], in conscious rats.

Journal article J Pharmacol Exp Ther · September 2004 This study provides novel data on the regional hemodynamic effects of the peroxisome proliferator-activated receptor-gamma activator, GI 262570 [(S)-2-(2-benzoylphenylamino)-3-[4-[2-(5-methyl-2-phenyl-2-oxazol-4-yl)ethoxy]phenyl]propionic acid], in conscio ... Full text Link to item Cite

Potential urinary and plasma biomarkers of peroxisome proliferation in the rat: identification of N-methylnicotinamide and N-methyl-4-pyridone-3-carboxamide by 1H nuclear magnetic resonance and high performance liquid chromatography.

Journal article Biomarkers · 2003 This study identified two potential novel biomarkers of peroxisome proliferation in the rat. Three peroxisome proliferator-activated receptor (PPAR) ligands, chosen for their high selectivity towards the PPARalpha, -delta and -gamma subtypes, were given to ... Full text Link to item Cite

Right ventricular hypertrophy secondary to pulmonary hypertension is linked to rat chromosome 17: evaluation of cardiac ryanodine Ryr2 receptor as a candidate.

Journal article Circulation · January 23, 2001 BACKGROUND: Fischer 344 (F344) rats are relatively resistant to hypoxia-induced right ventricular (RV) hypertrophy compared with the Wistar-Kyoto (WKY) strain. These 2 strains were used to examine the genetic basis for the differential response. METHODS AN ... Full text Link to item Cite

Genetic determination of cardiac mass in normotensive rats: results from an F344xWKY cross.

Journal article Hypertension · April 1999 Genetic determinants affect adult cardiac mass and the predisposition to develop cardiac hypertrophy. The aim of this study was to identify quantitative trait loci (QTL) that control heart and left ventricular (LV) weight by use of normotensive inbred rat ... Full text Link to item Cite

Human beta-myosin heavy chain mRNA prevalence is inversely related to the degree of methylation of regulatory elements.

Journal article Cardiovasc Res · June 1998 OBJECTIVE: Methylation of cytosine in CG dinucleotides within regulatory elements is believed to silence gene expression. These dinucleotides occur in certain important regulatory elements in the promoter region of the human beta-myosin heavy chain (beta-M ... Full text Link to item Cite

Downregulation of natriuretic peptide C-receptor protein in the hypertrophied ventricle of the aortovenocaval fistula rat.

Journal article Cardiovasc Res · December 1997 OBJECTIVES: This study examined the expression of the C-type receptor for the natriuretic peptide family (NPR-C) in the ventricles of normal and aortovenocaval (AV)-fistula rats, the latter a model of cardiac volume overload producing hypertrophy of both v ... Full text Link to item Cite

Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung.

Journal article Br J Pharmacol · November 1996 1. Angiotensin II (AII) binding density and the effect of chronic AII receptor blockade were examined in the rat model of hypoxia-induced pulmonary hypertension. 2. [125I]-[Sar1,Ile2]AII binding capacity was increased in lung membranes from rats exposed to ... Full text Link to item Cite

Adrenomedullin activity in chronically hypoxic rat lungs.

Journal article Am J Physiol · August 1996 Adrenomedullin (AM) is a novel vasodilator with structural similarities to calcitonin gene-related peptide (CGRP). This study investigated AM activity in the rat lung during hypoxia-induced pulmonary hypertension. Both rat AM (0.2-10 nmol) and alpha-CGRP ( ... Full text Link to item Cite

Hypertensive cardiac hypertrophy--is genetic variance the missing link?

Journal article Br J Clin Pharmacol · July 1996 1. Hypertensive cardiac hypertrophy is a major independent predictor of adverse cardiovascular events. In man the cardiac response to increased afterload is very variable, even when ambulatory blood pressure monitoring is used. Analysis of breeding experim ... Full text Link to item Cite

Messenger RNAs encoding the natriuretic peptides and their receptors are expressed in the eye.

Journal article Exp Eye Res · December 1995 The rates of secretion and removal of aqueous humour are major determinants of intraocular pressure (IOP). The natriuretic peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are vasodilators wit ... Full text Link to item Cite

Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aorto-venacaval fistula rat.

Journal article Cardiovasc Res · June 1995 OBJECTIVE: At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) ... Link to item Cite

Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat.

Journal article J Clin Invest · December 1993 The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C. We have examined the temporal relationship between the expression of mRNA transcripts for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP ... Full text Link to item Cite

Natriuretic peptide receptor mRNAs in the rat and human heart.

Journal article J Clin Invest · November 1992 Functional studies indicate that atrial natriuretic peptide (ANP), a member of the natriuretic peptide family, has direct effects on cardiac muscle cells. However, conventional ligand-binding studies designed to establish the presence of natriuretic peptid ... Full text Link to item Cite

c-fos may code for a common transcription factor within the hypothalamic neural circuits involved in osmoregulation.

Journal article Brain Res · February 14, 1992 Conscious rats were given an intraperitoneal (i.p.) injection of isotonic or hypertonic saline, and killed 10-240 min later. In the hypothalamus of hypertonic saline-injected rats, c-fos-mRNA positive cells were mainly restricted to the supraoptic and para ... Full text Link to item Cite

Endothelin-1 mRNA expression in the rat kidney.

Journal article Biochem J · May 1, 1991 Cultured pig and bovine endothelial cells are capable of synthesizing endothelin-1 (ET-1). Thus the observation that the kidney contains a large number of binding sites for ET distributed in close proximity to endothelial cells suggests that ET-1 may be re ... Full text Link to item Cite

Atrial natriuretic factor mRNA and binding sites in the adrenal gland.

Journal article Biochem J · October 15, 1990 The factor inhibiting aldosterone secretion produced by the adrenal medulla may be atrial natriuretic factor (ANF), since the latter abolishes aldosterone release in response to a number of secretagogues, including angiotensin II and K+. In this study we h ... Full text Link to item Cite

Endothelin-1 mRNA is widely expressed in porcine and human tissues.

Journal article J Clin Invest · May 1990 Endothelin-1 (ET-1) is a potent vasoconstrictor peptide isolated from porcine endothelial cells. We have previously demonstrated widespread binding sites for ET-1 in blood vessels, heart, kidney, adrenal, lung, and brain in a distribution that paralleled t ... Full text Link to item Cite

A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma: comparison of levels in patients with essential hypertension and normotensive control subjects.

Journal article Clin Sci (Lond) · March 1990 1. A radioimmunoassay has been developed for measuring endothelin-like immunoreactivity in human plasma using an antibody raised against endothelin-1 which also cross-reacts with big endothelin-1 and endothelin-2 but not endothelin-3. 2. The sensitivity of ... Full text Link to item Cite

A quantitative 'in-situ' hybridization method using computer-assisted image analysis. Validation and measurement of atrial-natriuretic-factor mRNA in the rat heart.

Journal article Biochem J · October 1, 1989 We have validated a quantitative 'in-situ' hybridization method and computer-assisted image analysis of autoradiographs as a technique for measuring atrial-natriuretic-factor (ANF) mRNA in tissue sections of rat heart by: (i) producing radioactive standard ... Full text Link to item Cite

Binding sites for 125I-labelled endothelin-1 in the kidneys: differential distribution in rat, pig and man demonstrated by using quantitative autoradiography.

Journal article Clin Sci (Lond) · August 1989 1. Quantitative receptor autoradiography in vitro has been used to determine the distribution and density of specific binding sites for 125I-labelled endothelin-1 in human, porcine and rat kidneys. Immunocytochemistry was used to visualize von Willebrand f ... Full text Link to item Cite

THE HYPOTHALAMUS

Journal article CURRENT OPINION IN NEUROLOGY AND NEUROSURGERY · August 1989 Link to item Cite

Autoradiographical localization of binding sites for porcine [125I]endothelin-1 in humans, pigs, and rats: functional relevance in humans.

Journal article J Cardiovasc Pharmacol · 1989 Endothelin-1 (ET-1) is a recently discovered 21 amino acid peptide with potent vasoconstrictor properties. So far, its expression has been found only in porcine aorta, whereas its putative role as the endothelium-derived constricting factor (EDCF) would re ... Full text Link to item Cite