Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2
- Gwen Tolhurst1,
- Helen Heffron2,
- Yu Shan Lam1,
- Helen E. Parker1,
- Abdella M. Habib1,
- Eleftheria Diakogiannaki1,
- Jennifer Cameron2,
- Johannes Grosse2,
- Frank Reimann1⇓ and
- Fiona M. Gribble1⇓
- 1Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, Addenbrooke’s Hospital, Cambridge, U.K.
- 2Takeda Cambridge Ltd, Cambridge, U.K.
- Corresponding authors: Fiona M. Gribble, , and Frank Reimann, .
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.
- Received July 21, 2011.
- Accepted November 5, 2011.
- © 2012 by the American Diabetes Association.
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