Back to Search
Start Over
TGR5-mediated bile acid sensing controls glucose homeostasis
- Source :
- Cell Metab, Cell Metab, 2009, 10 (3), pp.167-77. ⟨10.1016/j.cmet.2009.08.001⟩, Cell metabolism
- Publication Year :
- 2009
-
Abstract
- International audience; 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.
- Subjects :
- Male
Physiology
HUMDISEASE
Mice, Obese
Enteroendocrine cell
Oxidative Phosphorylation
Receptors, G-Protein-Coupled
Mice
Adenosine Triphosphate
0302 clinical medicine
Glucagon-Like Peptide 1
Cricetinae
Brown adipose tissue
energy expenditure
Homeostasis
Insulin
Glucose homeostasis
ADP/ATP
Mice, Knockout
0303 health sciences
Bile acid
Tgr5
Cell-Line
G protein-coupled bile acid receptor
medicine.anatomical_structure
Fxr
INT-777
Signal transduction
Derivatives
Signal Transduction
medicine.medical_specialty
TGR-5
semi-synthetic bile acid
GLP-1
diabesity
medicine.drug_class
Enteroendocrine Cells
Activation
Incretin
030209 endocrinology & metabolism
CHO Cells
Biology
Cell Line
Farnesoid-X-Receptor
Bile Acids and Salts
03 medical and health sciences
Cricetulus
Internal medicine
Protein-Coupled Receptor
medicine
Animals
Humans
Energy-Expenditure
Molecular Biology
030304 developmental biology
Cholic Acids
Cell Biology
Mice, Inbred C57BL
Peptide-1 Secretion
Glucose
Endocrinology
Calcium
Farnesoid X receptor
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Metab, Cell Metab, 2009, 10 (3), pp.167-77. ⟨10.1016/j.cmet.2009.08.001⟩, Cell metabolism
- Accession number :
- edsair.doi.dedup.....93fe31fa4d4a67986eb45cc2cabb4efe