Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 64, Issue 9, Pages 647-651Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2010.06.008
Keywords
GPR40; Antagonist; Insulin tolerance; Glucose tolerance; Diabetes
Funding
- National Science & Technology Major Project [2009ZX09301-001, 2009ZX09501-001]
- National High Technology Research and Development Program of China (863 Program) [2007AA02Z301]
- Shanghai Science and Technology Innovation Program [08431900800]
- Shanghai institutions of higher learning
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GPR40 is a G-protein-coupled receptor specifically expressed in pancreatic islets, which maybe mediate both acute and chronic effects of free fatty acids (FFAs) on beta-cell function. However, it is still a matter of debate whether GPR40 represents a novel therapeutic target for type 2 diabetes. To this aim, we evaluated the effect of DC260126, a small-molecule antagonist of GPR40, on glucose and lipid metabolism in obese Zucker rats. Rats were treated intraperitoneally with 6 mg/kg of DC260126 for 8 weeks. DC260126 could significantly decrease serum insulin levels, improve insulin tolerance and increase Akt phosphorylation levels in liver, suggesting improved insulin sensitivity in DC260126-treated rats. However, DC260126 did not affect food intake, body weight, blood glucose and lipids. Throughout the experimental period, no significant difference in glucose tolerance was observed between the vehicle and DC260126-treated rats. These results indicate that GPR40 antagonists may not be beneficial for the treatment of type 2 diabetes, although GPR40 antagonists could improve insulin tolerance and increase insulin signaling in vivo. (C) 2010 Elsevier Masson SAS. All rights reserved.
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