TGR5-mediated bile acid sensing controls glucose homeostasis. - Archive ouverte HAL Access content directly
Journal Articles Cell Metab Year : 2009

TGR5-mediated bile acid sensing controls glucose homeostasis.

(1) , (2) , (1, 3) , (1) , (1) , (4) , (2) , (1, 3) , (1, 3) , (4) , (2) , (1, 3, 5) , (3)
1
2
3
4
5

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.

Dates and versions

inserm-00420823 , version 1 (29-09-2009)

Identifiers

Cite

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⟩
442 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More