Horm Metab Res 2011; 43(3): 226-228
DOI: 10.1055/s-0030-1267227
Short Communication

© Georg Thieme Verlag KG Stuttgart · New York

Combination Therapy with Nateglinide and Telmisartan Ameliorates Insulin Resistance in Zucker Fatty Rats by Suppressing Advanced Glycation End Product Receptor Axis

K. Miura1 , Y. Kitahara1 , T. Kajioka1 , M. Takeuchi2 , S. Yamagishi3
  • 1Exploratory Research Laboratories, Ajinomoto Pharmaceuticals Co. Ltd., Kawasaki, Japan
  • 2Department of Life Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
  • 3Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
Further Information

Publication History

received 12.08.2010

accepted 20.09.2010

Publication Date:
22 October 2010 (online)

Abstract

Advanced glycation end products (AGEs) and their receptor (RAGE) have been shown to play a role in insulin resistance. We have previously shown that combination therapy with nateglinide (NAT) and telmisartan (TEL) improves postprandial metabolic derangements in Zucker fatty (ZF) rats, an animal model of insulin resistance with obesity. However, effects of combination therapy on insulin resistance remain unknown. We investigated here whether combination therapy with TEL and NAT could ameliorate insulin resistance in ZF rats by suppressing AGE-RAGE axis. NAT and/or TEL inhibited insulin receptor substrate-1 (IRS-1) serine phosphorylations at 307 and 636/639 residues in the liver of ZF rats. Further, combination therapy with NAT and TEL, but not each monotherapy alone, significantly restored the decrease in hepatic IRS-1 tyrosine phosphorylation in these animals. In addition, serum levels of AGEs, RAGE expression levels in the liver and hepatic AGE-RAGE index were decreased in NAT plus TEL-treated ZF rats. The present study suggests that combination therapy with NAT and TEL could ameliorate insulin resistance in ZF rats by suppressing the AGE-RAGE axis in the liver.

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Notice:

This article was changed according to the following erratum on November 16th, 2010: One of the authors' name is misspelt. The correct name is M. Takeuchi.

Correspondence

S. YamagishiMD, PhD 

Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications

Kurume University School of Medicine

67 Asahi-machi

Kurume 830-0011

Japan

Phone: +81/942/31 7873

Fax: +81/942/31 7873

Email: shoichi@med.kurume-u.ac.jp