TGR5-mediated bile acid sensing controls glucose homeostasis.
Cell Metab
; 10(3): 167-77, 2009 Sep.
Article
en En
| MEDLINE
| ID: mdl-19723493
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.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Ácidos y Sales Biliares
/
Ácidos Cólicos
/
Receptores Acoplados a Proteínas G
/
Glucosa
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2009
Tipo del documento:
Article
País de afiliación:
Francia