Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2
By G. Tolhurst, H. Heffron, Yu Shan Lam, H. Parker, A. Habib, Eleftheria Diakogiannaki, J. Cameron, J. Grosse, F. Reimann, F. Gribble. Diabetes, 2012
2,064 citations recorded by the source corpus.
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.
Subfields: Endocrinology, Diabetes and Metabolism, Genetics, Surgery
View Paper: https://www.semanticscholar.org/paper/02cee3c58d4eff6cff85f2478e9f61acf0529768
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Citations in the corpus
- Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances (2016, background): “In particular, SCFAs interact with G-protein-coupled receptors (GPCRs) to regulate fat deposition (Samuel et al., 2008), and improve insulin secretion through modulation of the levels of the GLP1 hormone (Tolhurst et al., 2012).”
- Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota (2023, background): “Moreover, the action of those two receptors may influence the energy consumption of neurons [30], insulin secretion from Langerhans islets beta cells [31,32] and enteroendocrine function [33,34].”