A5014392022- Diabetes Treatment and Management
- Pancreatic function and diabetes
- Regulation of Appetite and Obesity
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Biochemical Analysis and Sensing Techniques
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Receptor Mechanisms and Signaling
- Dietary Effects on Health
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Neuroendocrine Tumor Research Advances
- Diabetes Management and Research
- Advancements in Transdermal Drug Delivery
- Pharmacology and Obesity Treatment
- Polysaccharides Composition and Applications
- Muscle metabolism and nutrition
- Signaling Pathways in Disease
- Pregnancy and preeclampsia studies
- Sleep and Wakefulness Research
- Curcumin's Biomedical Applications
- Nitric Oxide and Endothelin Effects
Abbott (Singapore)
2011-2016
National University of Singapore
2016
Clinical Nutrition Research Centre
2016
Laboratoire de Biochimie
2011
KineMed (United States)
2008-2010
Oregon Health & Science University
2010
University of California, Berkeley
2010
Albert Einstein College of Medicine
2003-2009
Children's Hospital at Montefiore
2009
University of Washington
2002-2008
Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic α cells in response low blood glucose. To examine role of glucagon glucose homeostasis, mice were generated with a null mutation receptor (Gcgr −/− ). These display lower levels throughout day and improved tolerance but similar insulin compared control animals. Gcgr displayed supraphysiological associated postnatal enlargement pancreas hyperplasia islets due predominantly cell, lesser extent, δ cell...
The capacity to adjust energy intake in response changing requirements is a defining feature of homeostasis. Despite the identification leptin as key mediator this process, mechanism whereby changes body adiposity are coupled adaptive, short-term adjustments remains poorly understood. To investigate physiological role control meal size and satiety signals, identify brain areas mediating effect, we studied Koletsky (fak/fak) rats, which develop severe obesity due genetic absence receptors....
Phosphatidylinositol 3-OH-kinase (PI3K) and STAT3 are signal transduction molecules activated by leptin in brain areas controlling food intake. To investigate their role leptin-mediated inhibition of hypothalamic neuropeptide Y (Npy) agouti-related peptide (Agrp) gene expression, male Sprague-Dawley rats (n = 5/group) were either fed ad libitum or subjected to a 52-h fast. At 12-h intervals, the PI3K inhibitor LY-294002 (LY, 1 nmol) vehicle was injected intracerebroventricularly (ICV) as...
The capacity to adjust energy intake in response changing requirements is a defining feature of homeostasis. Despite the identification leptin as key mediator this process, mechanism whereby changes body adiposity are coupled adaptive, short-term adjustments remains poorly understood. To investigate physiological role control meal size and satiety signals, identify brain areas mediating effect, we studied Koletsky (fak/fak) rats, which develop severe obesity due genetic absence receptors....
Incretins are endogenous peptides released from the gastrointestinal tract into circulation during a meal that potentiate glucose-stimulated insulin secretion. At present, there two established incretins: glucose-dependent insulinotropic polypeptide (GIP) and truncated glucagon-like (tGLPs), which now being investigated for use in treatment of diabetes mellitus. In present study we cloned rat islet GIP receptor complementary DNA (GIP-R1) to answer several important questions regarding...
Although glucagon (GLU) plays a pivotal role in glucose homeostasis, its the regulation of fetal growth and maturation is poorly understood. These issues were examined line mice with global deletion GLU receptor (Gcgr−/−), which are characterized by lower blood levels α- δ-cell hyperplasia adults. Ablation Gcgr was deleterious to survival; it delayed β-cell differentiation perturbed proportion β- α-cells embryonic islets. In adults, mutation inhibited progression maturity, affected...
In previous studies, glucagon receptor knockout mice (Gcgr(-/-)) display reduced blood glucose and increased tolerance, with hyperglucagonemia levels of glucagon-like peptide (GLP)-1. However, the role signaling for regulation islet function insulin sensitivity is unknown. We therefore explored beta-cell in Gcgr(-/-) wild-type mice. The steady-state infusion rate during hyperinsulinemic-euglycemic clamp was elevated mice, indicating enhanced sensitivity. Furthermore, acute response (AIR) to...
The therapeutic potential of glucose-dependent insulinotropic polypeptide (GIP) for improving glycemic control has largely gone unstudied. A series synthetic GIP peptides modified at the NH2-terminus were screened in vitro resistance to dipeptidyl peptidase IV (DP IV) degradation and potency stimulate cyclic AMP affinity transfected rat receptor. In experiments indicated that [d-Ala2]GIP possessed greatest enzymatic degradation, combined with minimal effects on efficacy Thus, [d-Ala2]GIP1–42...
Evidence suggests that release of oxytocin in the nucleus tractus solitarius (NTS) hindbrain from descending projections originate paraventricular can inhibit food intake by amplifying satiety response to cholecystokinin (CCK). To further evaluate this mechanism rats, we used a novel cytotoxin, saporin conjugated (OXY-SAP), compound designed destroy cells express receptors (OXYr). OXY-SAP was injected directly into NTS lesion neurons OXYr and are implicated potentiating CCK’s effects. The...
Plasma levels of the orexigenic hormone, ghrelin, decrease rapidly on nutrient ingestion and yet are paradoxically elevated in rats with hyperphagia induced by streptozotocin-induced diabetes (STZ-DM). In current work, we investigated mechanisms underlying relationships among uncontrolled diabetes, food intake, plasma ghrelin concentrations an effort to clarify whether increased signaling contributes diabetic hyperphagia. Whereas intake did not increase until d 3 after STZ administration,...
Energy homeostasis involves central nervous system integration of afferent inputs that coordinately regulate food intake and energy expenditure. Here, we report adult homozygous TNFalpha converting enzyme (TACE)-deficient mice exhibit one the most dramatic examples hypermetabolism yet reported in a rodent system. Because this effect is not matched by increased intake, lacking TACE lean phenotype. In hypothalamus these mice, neurons arcuate nucleus intact responses to reduced fat mass low...
In addition to its primary role in regulating glucose production from the liver, glucagon has many other actions, reflected by wide tissue distribution of receptor (Gcgr). To investigate regulation insulin secretion and whole body homeostasis vivo, we generated mice overexpressing Gcgr specifically on pancreatic beta-cells (RIP-Gcgr). vivo vitro response was increased 1.7- 3.9-fold RIP-Gcgr compared with controls. Consistent observed increase release glucose, excursion resulting both a...
Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which turn increase glycogenolysis as well gluconeogenesis and ureagenesis from amino acids. Conversely, secretion is regulated concentrations of Disruption signaling rodents results grossly elevated circulating levels but no hypoglycemia. Here, we describe a patient carrying homozygous G to A substitution invariant AG dinucleotide found 3' mRNA splice junction receptor gene. Loss site...
Scope High-fat diet (HFD) induces overeating and obesity. Green tea (-)-epigallocatechin-3-gallate (EGCG) reduces HFD-induced body weight fat gain mainly through increased lipid metabolism oxidation. However, little is known about its effect on alterations in feeding behavior. Methods results Three groups of wildtype C57B/6j male mice at 5 months old were fed normal chow diet, 1 week HFD (60% energy) 3 (diet-induced obesity (DIO)) prior to EGCG supplement respective diet. had no behavior...
GIP is an important insulinotropic hormone (incretin) that has also been implicated in fat metabolism. There controversy regarding the actions of on adipocytes. In current study, existence receptors and effects lipolysis were studied differentiated 3T3-L1 cells. receptor messenger RNA was detected by RT-PCR RNase protection assay. Receptors binding studies (IC50 26.7 +/- 0.7 nM). stimulated glycerol release with EC50 3.28 0.63 nM. (10(-9)-10(-7) M) IBMX increased cAMP production 1180-2246%....
Alterations in insulin signaling as well action predispose to infertility adverse pregnancy outcomes; however, little is known about the role of glucagon reproduction. The receptor knockout (Gcgr(-/-)) mouse created by our laboratory was used define maintaining normal In this model, lack did not alter hypothalamic-pituitary-ovarian axis. Pregnant Gcgr(-/-) female mice displayed persistent hypoglycemia and hyperglucagonemia. pregnancies were associated with decreased fetal weight, increased...
The receptors for the two structurally related insulinotropic hormones Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) share approximately 40% sequence identity demonstrate complete specificity their endogenous ligands, while utilizing similar second messsenger pathways. In current study chimeric GIP-GLP-1 were prepared, effect of domain-exchange on ligand binding adenylyl cyclase activation examined. A chimera (CH-2) consisting first 132 amino acids...
Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone involved in the regulation of insulin secretion. In non-insulin-dependent diabetes mellitus responses to GIP are blunted, possibly due altered signal transduction or reduced receptor number. Site-directed mutagenesis was used construct truncated receptors study importance carboxyl-terminal tail (CT) binding, signaling, and internalization. Receptors at amino acids 425, 418, 405, expressed COS-7 CHO-K1 cells,...