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TGR5-mediated bile acid sensing controls glucose homeostasis.

Abstract : TGR5 is a G protein-coupled receptor expressed in brown adipose tissue and muscle, where its activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity. Using a combination of pharmacological and genetic gain- and loss-of-function studies in vivo, we show here that TGR5 signaling induces intestinal glucagon-like peptide-1 (GLP-1) release, leading to improved liver and pancreatic function and enhanced glucose tolerance in obese mice. In addition, we show that the induction of GLP-1 release in enteroendocrine cells by 6alpha-ethyl-23(S)-methyl-cholic acid (EMCA, INT-777), a specific TGR5 agonist, is linked to an increase of the intracellular ATP/ADP ratio and a subsequent rise in intracellular calcium mobilization. Altogether, these data show that the TGR5 signaling pathway is critical in regulating intestinal GLP-1 secretion in vivo, and suggest that pharmacological targeting of TGR5 may constitute a promising incretin-based strategy for the treatment of diabesity and associated metabolic disorders.
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Submitted on : Tuesday, September 29, 2009 - 4:55:20 PM
Last modification on : Thursday, April 23, 2020 - 2:26:35 PM

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Charles Thomas, Antimo Gioiello, Lilia Noriega, Axelle Strehle, Julien Oury, et al.. TGR5-mediated bile acid sensing controls glucose homeostasis.. Cell Metab, 2009, 10 (3), pp.167-77. ⟨10.1016/j.cmet.2009.08.001⟩. ⟨inserm-00420823⟩



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