Journal article
GPR41 modulates insulin secretion and gene expression in pancreatic -cells and modifies metabolic homeostasis in fed and fasting states
FASEB Journal, Vol.30(11), pp.3860-3869
Nov/2016
Abstract
Insulin secretion by pancreatic -cells is primarily regulated by glucose; however, hormones and additional nutrients, such as long-chain fatty acids, also play an important role in adjusting insulin output to physiologic needs. To examine the role of short-chain fatty acids (SCFAs) in -cell function, we analyzed mouse models of gain and loss of function of GPR41 (FFAR3), a receptor for SCFAs, vs. wild-type control mice. GPR41 gain of function [GPR41-overexpressing transgenic (41 Tg) model] and GPR41 loss of function [GPR41-knockout (KO 41) model] resulted in complementary changes in glucose tolerance, without significant effects on insulin sensitivity. KO 41 mice showed fasting hypoglycemia, which was consistent with increased basal and glucose-induced insulin secretion by islets in vitro. Mirroring this, 41 Tg islets showed impaired glucose responsiveness in vitro. Microarray analysis of islets from 41 Tg mice indicated significant alterations in gene expression patterns; several of the altered genes were chosen for further analysis and were also observed to change upon incubation of islets and cultured -cells with SCFAs in a GPR41-dependent manner. Taken together, our results indicate that GPR41 and its ligands, SCFAs, may play an important role in the fine-tuning of insulin secretion in fed and fasting states.Veprik, A., Laufer, D., Weiss, S., Rubins, N., Walker, M. D. GPR41 modulates insulin secretion and gene expression in pancreatic -cells and modifies metabolic homeostasis in fed and fasting states.
Details
- Title
- GPR41 modulates insulin secretion and gene expression in pancreatic -cells and modifies metabolic homeostasis in fed and fasting states
- Creators
- Anna Veprik (null) - 972WIS_INST___112Dana Laufer (null) - The Weizmann Institute of ScienceSara Weiss (null) - The Weizmann Institute of ScienceNir Rubins (null) - The Weizmann Institute of ScienceMichael Walker (Corresponding Author) - 972WIS_INST___112
- Resource Type
- Journal article
- Publication Details
- FASEB Journal, Vol.30(11), pp.3860-3869; Nov/2016
- Number of pages
- 10
- Language
- English
- DOI
- https://doi.org/10.1096/fj.201500030R
- Grant note
- The authors thank H. Shapiro (Weizmann Institute) for valuable advice and suggestions, S. Ben‐Dor (Weizmann Institute) for bioinformatic analysis, A. Brandis (Weizmann Institute) for SCFA analyses, B. Glaser (Hebrew University, Jerusalem, Israel) and Y. Dor (Hebrew University) for valuable discussions, J. Gordon (Washington University) and M. Yanagisawa (University of Texas, Southwestern Medical Center, Dallas, TX, USA) for generously providing GPR41 KO mice, A. Eisenberg‐Lerner (Weizmann Institute) and O. Elhanani (Weizmann Institute) for assistance with in vitro experiments, and V. Kiss (Weizmann Institute) and R. Nevo (Weizmann Institute) for assistance with microscopy and image analysis. M.D.W. is incumbent of the Marvin Meyer and Jenny Cyker Chair of Diabetes Research at the Weizmann Institute. A. Veprik performed most of the experiments, analyzed and interpreted data, and wrote the manuscript; D. Laufer participated in some of the in vivo and in vitro experiments; S. Weiss participated in some of the in vivo experiments; N. Rubins generated 41 Tg mice; and M. D. Walker supervised the project, analyzed and interpreted data, and wrote the manuscript.
- Record Identifier
- 993263514503596
Metrics
11 Record Views