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Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets.
Mol Cell Endocrinol. 2015 Mar 15; 404:56-66.MC

Abstract

The 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 downstream 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 (ΔΨm), but with increased expression of uncoupling protein 2 (Ucp2), Pparg and Gpr109a in INS-1E cells. Corroborating these findings, the decreases in GSIS, ΔΨm 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-PPARγ-UCP2 pathways.

Authors+Show Affiliations

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.Centre for Diabetes, The Blizard Institute, Queen Mary University of London, London, UK.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: psleung@cuhk.edu.hk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25622782

Citation

Chen, Lihua, et al. "Niacin-induced Hyperglycemia Is Partially Mediated Via Niacin Receptor GPR109a in Pancreatic Islets." Molecular and Cellular Endocrinology, vol. 404, 2015, pp. 56-66.
Chen L, So WY, Li SY, et al. Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets. Mol Cell Endocrinol. 2015;404:56-66.
Chen, L., So, W. Y., Li, S. Y., Cheng, Q., Boucher, B. J., & Leung, P. S. (2015). Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets. Molecular and Cellular Endocrinology, 404, 56-66. https://doi.org/10.1016/j.mce.2015.01.029
Chen L, et al. Niacin-induced Hyperglycemia Is Partially Mediated Via Niacin Receptor GPR109a in Pancreatic Islets. Mol Cell Endocrinol. 2015 Mar 15;404:56-66. PubMed PMID: 25622782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets. AU - Chen,Lihua, AU - So,Wing Yan, AU - Li,Stephen Y T, AU - Cheng,Qianni, AU - Boucher,Barbara J, AU - Leung,Po Sing, Y1 - 2015/01/23/ PY - 2014/01/08/received PY - 2015/01/20/revised PY - 2015/01/20/accepted PY - 2015/1/28/entrez PY - 2015/1/28/pubmed PY - 2015/12/15/medline KW - G-protein coupled receptor KW - Glucose homeostasis KW - Insulin secretion KW - Islet function KW - Pancreas KW - Reactive oxygen species SP - 56 EP - 66 JF - Molecular and cellular endocrinology JO - Mol Cell Endocrinol VL - 404 N2 - The 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 downstream 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 (ΔΨm), but with increased expression of uncoupling protein 2 (Ucp2), Pparg and Gpr109a in INS-1E cells. Corroborating these findings, the decreases in GSIS, ΔΨm 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-PPARγ-UCP2 pathways. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/25622782/Niacin_induced_hyperglycemia_is_partially_mediated_via_niacin_receptor_GPR109a_in_pancreatic_islets_ DB - PRIME DP - Unbound Medicine ER -