A Novel TGR5 Activator WB403 Promotes GLP-1 Secretion and Preserves Pancreatic β-Cells in Type 2 Diabetic Mice.

ABSTRACT: The G protein-coupled receptor TGR5 is a membrane receptor for bile acids. Its agonism increases energy expenditure and controls blood glucose through secretion of glucagon-like peptide-1 in enteroendocrine cells. In this study, we explored the therapeutic potential of WB403, a small compound activating TGR5 which was identified by combining TGR5 targeted luciferase assay and active GLP-1 assay, in treating type 2 diabetes. After confirmation of TGR5 and GLP-1 stimulating activities in various cell systems, WB403 was examined in oral glucose tolerance test, and tested on different mouse models of type 2 diabetes for glycemic control and pancreatic β-cell protection effect. As a result, WB403 exhibited a moderate TGR5 activation effect while promoting GLP-1 secretion efficiently. Interestin

SUBMITTER: Zheng C 

PROVIDER: S-EPMC4514850 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature