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Signal Transduction

Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2

  1. Gwen Tolhurst1,
  2. Helen Heffron2,
  3. Yu Shan Lam1,
  4. Helen E. Parker1,
  5. Abdella M. Habib1,
  6. Eleftheria Diakogiannaki1,
  7. Jennifer Cameron2,
  8. Johannes Grosse2,
  9. Frank Reimann1⇓ and
  10. Fiona M. Gribble1⇓
  1. 1Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, Addenbrooke’s Hospital, Cambridge, U.K.
  2. 2Takeda Cambridge Ltd, Cambridge, U.K.
  1. Corresponding authors: Fiona M. Gribble, fmg23{at}cam.ac.uk, and Frank Reimann, fr222{at}cam.ac.uk.
  1. G.T. and H.H. contributed equally to this work.

Diabetes 2012 Feb; 61(2): 364-371. https://doi.org/10.2337/db11-1019
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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.

  • Received July 21, 2011.
  • Accepted November 5, 2011.
  • © 2012 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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February 2012, 61(2)
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Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2
Gwen Tolhurst, Helen Heffron, Yu Shan Lam, Helen E. Parker, Abdella M. Habib, Eleftheria Diakogiannaki, Jennifer Cameron, Johannes Grosse, Frank Reimann, Fiona M. Gribble
Diabetes Feb 2012, 61 (2) 364-371; DOI: 10.2337/db11-1019

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Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2
Gwen Tolhurst, Helen Heffron, Yu Shan Lam, Helen E. Parker, Abdella M. Habib, Eleftheria Diakogiannaki, Jennifer Cameron, Johannes Grosse, Frank Reimann, Fiona M. Gribble
Diabetes Feb 2012, 61 (2) 364-371; DOI: 10.2337/db11-1019
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