Horm Metab Res 2007; 39(12): 889-893
DOI: 10.1055/s-2007-992798
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Potential Utility of Combination Therapy with Nateglinide and Telmisartan for Metabolic Derangements in Zucker Fatty Rats

T. Kajioka 1 , K. Miura 1 , Y. Kitahara 1 , S. Yamagishi 2
  • 1Pharmaceutical Research Laboratories, Ajinomoto, Kawasaki, Japan
  • 2Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, Kurume, Japan
Further Information

Publication History

received 04.12.2006

accepted 10.05.2007

Publication Date:
07 November 2007 (online)

Abstract

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular disease. Insulin resistance and/or impaired early-phase insulin secretion are major determinants of postprandial hyperglycemia. In this study, we investigated the potential utility of combination therapy with telmisartan, an angiotensin II receptor blocker and nateglinide, a rapid-onset/short-duration insulinotropic agent, for the treatment of postprandial hyperglycemia and metabolic derangements in Zucker Fatty (ZF) rats. ZF rats fed twice daily were given vehicle, 50 mg/kg of nateglinide, 5 mg/kg of telmisartan, or both for 6 weeks. Combination therapy with nateglinide and telmisartan for 2 weeks ameliorated postprandial hyperglycemia in ZF rats fed twice daily. Furthermore, 6-week treatment with nateglinide and telmisartan not only decreased fasting plasma insulin, triglycerides, and free fatty acid levels, but also improved the responses of blood glucose to insulin and subsequently reduced the decremental glucose areas under the curve in the ZF rats. Combination therapy also restored the decrease of plasma adiponectin levels in the ZF rats. Monotherapy with nateglinide or telmisartan alone didnot significantly improve these metabolic parameters. These observations demonstrate that combination therapy with nateglinide and telmisartan may improve the metabolic derangements by ameliorating early phase of insulin secretion as well as insulin resistance in ZF rats fed twice daily. Our present findings suggest that the combination therapy with nateglinide and telmisartan could be a promising therapeutic strategy for the treatment of the metabolic syndrome.

References

Correspondence

S. Yamagishi, MD, PhD 

Department of Medicine

Division of Cardiovascular Medicine

Kurume University School of Medicine

67 Asahi-machi

830-0011 Kurume

Japan

Phone: +81/942/31 75 80

Fax: +81/942/31 77 07

Email: [email protected]