| First Author | Thomas C | Year | 2009 |
| Journal | Cell Metab | Volume | 10 |
| Issue | 3 | Pages | 167-77 |
| PubMed ID | 19723493 | Mgi Jnum | J:152388 |
| Mgi Id | MGI:4358635 | Doi | 10.1016/j.cmet.2009.08.001 |
| Citation | Thomas C, et al. (2009) TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 10(3):167-77 |
| abstractText | 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. |
