Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2
Top Cited Papers
Open Access
- 17 January 2012
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 61 (2), 364-371
- https://doi.org/10.2337/db11-1019
Abstract
Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of “indigestible” prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1–secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.Keywords
This publication has 33 references indexed in Scilit:
- Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acidsFEBS Letters, 2010
- Postprandial Diabetic Glucose Tolerance Is Normalized by Gastric Bypass Feeding as Opposed to Gastric Feeding and Is Associated With Exaggerated GLP-1 SecretionDiabetes Care, 2009
- Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics) – preclinical and clinical resultsBest Practice & Research Clinical Endocrinology & Metabolism, 2009
- Expression of short-chain fatty acid receptor GPR41 in the human colonBiomedical Research, 2009
- Glucose Sensing in L Cells: A Primary Cell StudyCell Metabolism, 2008
- Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodentsAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41Proceedings of the National Academy of Sciences of the United States of America, 2008
- RD Lawrence Lecture 2008 Targeting GLP‐1 release as a potential strategy for the therapy of Type 2 diabetesDiabetic Medicine, 2008
- The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetesThe Lancet, 2006
- Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestineCell and tissue research, 2006