Combination therapy with nateglinide and vildagliptin improves postprandial metabolic derangements in Zucker fatty rats

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme
Kyoko MiuraS Yamagishi

Abstract

Postprandial metabolic derangements are one of the risk factors of cardiovascular disease in humans. Insulin resistance and/or impaired early-phase insulin secretion are major determinants of postprandial metabolic derangements. In this study, we investigated the potential utility of combination therapy with vildagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor and nateglinide, a rapid-onset/short-duration insulinotropic agent, for the treatment of postprandial metabolic derangements in Zucker Fatty (ZF) rats, an animal model of obesity with insulin resistance. ZF rats fed twice daily with or without high fat diet (HFD) were given vehicle, 50 mg/kg of nateglinide, 10 mg/kg of vildagliptin, or both for 6 weeks. Combination therapy with nateglinide and vildagliptin for 2 weeks ameliorated postprandial hyperglycemia, hypertriglyceridemia, and elevation of free fatty acid in ZF rats fed with HFD. 6-week treatment with nateglinide and vildagliptin not only increased hepatic levels of phosphorylated forkhead box protein 1A (FOXO1A), but also reduced triglyceride contents in the liver. Combination therapy also prevented the loss of pancreatic islet mass in ZF rats fed with HFD. These observations demonstrate that combination ther...Continue Reading

Citations

Feb 16, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Takanori MatsuiSho-ichi Yamagishi
Jul 24, 2013·Journal of Gastroenterology and Hepatology·Detlef Schuppan, Jörn M Schattenberg
Aug 16, 2016·Drug Development Research·Rowaida RefaatAshgan El Sarha
Jun 13, 2012·Clinical Pharmacokinetics·Larry K GolightlyMichael T McDermott

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