Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets
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AbstractThe widely used lipid-lowering drug niacin is reported to induce hyperglycemia during chronic and high-dose treatments, but the mechanism is poorly understood. Recently, the niacin receptor [G-protein-coupled receptor, (GPR) 109a], has been localized to islet cells while its potential role therein remains unclear. We, therefore, aimed at investigating how GPR109a regulates islet beta-cell function and its down-stream signaling using high-fat diet-induced obese mice and INS-1E beta cells. Eight-week niacin treatment elevated blood glucose concentration in obese mice with increased areas under the curve at oral glucose and intraperitoneal insulin tolerance tests. Additionally, niacin treatment significantly decreased glucose-stimulated insulin secretion (GSIS) but induced peroxisome proliferator-activated receptor gamma (Pparg) and GPR109a expression in isolated pancreatic islets; concomitantly, reactive oxygen species (ROS) were transiently increased, with decreases in GSIS, intracellular cyclic adenosine monophosphate (cAMP) accumulation and mitochondrial membrane potential (Delta Psi m), but with increased expression of uncoupling protein 2 (Ucp2), Pparg and Gpr109a in INS-1E cells. Corroborating these findings, the decreases in GSIS Delta Psi m and CAMP production and increases in ROS, Pparg and GPR109a expression were abolished in INS-1E cells by GPR109a knockdown. Our data indicate that niacin-induced pancreatic islet dysfunction is probably modulated through activation of the islet beta-cell GPR109a-induced ROS-PPAR gamma-UCP2 pathways. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
All Author(s) ListChen LH, So WY, Li SYT, Cheng QN, Boucher BJ, Leung PS
Journal nameMolecular and Cellular Endocrinology
Detailed descriptionTo ORKTS: Li Yu Ting Stephen is a CUHK GPS student (Student ID: 1155043787).
Year2015
Month3
Day15
Volume Number404
Issue NumberC
PublisherELSEVIER IRELAND LTD
Pages56 - 66
ISSN0303-7207
LanguagesEnglish-United Kingdom
KeywordsG-protein coupled receptor; Glucose homeostasis; Insulin secretion; Islet function; Pancreas; Reactive oxygen species
Web of Science Subject CategoriesCell Biology; Endocrinology & Metabolism

Last updated on 2020-25-09 at 02:21