4.4 Article

Effect of telmisartan on the expression of cardiac adiponectin and its receptor 1 in type 2 diabetic rats

Journal

JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 63, Issue 1, Pages 87-94

Publisher

WILEY
DOI: 10.1111/j.2042-7158.2010.01157.x

Keywords

adiponectin receptor; cardiomyopathy; telmisartan; type 2 diabetes

Funding

  1. Shanxi Scholarship Council of China [2007-2044]
  2. Department of Personnel of Shanxi Province of China

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Objectives This study investigated the effect of telmisartan on the expression of cardiac adiponectin and its receptor 1 in type 2 diabetic rats. Methods Thirty-six male Wistar rats were randomly divided into control (C, n = 10) and diabetic (n = 26) groups. Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). After induction of diabetes, diabetic rats were again randomly divided into diabetic (D, n = 10) and diabetic treated (DT, n = 10) groups. Telmisartan (5 mg/kg/day) was administrated to diabetic treated rats by gavage for 12 weeks. Twelve weeks later, the heart function was investigated. Plasma and myocardial adiponectin levels were detected by enzyme-linked immunosorbent assay (ELISA). The cardiac mRNA expression of adiponectin receptor 1 (adipiR1) was assayed by reverse transcript-polymerase chain reaction (RT-PCR). The cardiac protein expression of adipiR1, AMP-activated protein kinase (AMPK)-alpha, phospho-AMPK-alpha (Thr172) and glucose transporter 4(GLUT4) was determined by Western blotting. Key findings The ratio of heart weight to body weight was significantly increased in diabetic rats compared with control. The decreased levels of plasma and myocardial adiponectin and the decreased protein and mRNA expression of myocardial adipoR1 led to the decreased myocardial phosphorylation of AMPK-alpha (Thr172) and the decreased protein expression of myocardial GLUT4 in diabetic rats. Consequently, the heart function was decreased in diabetic rats. Telmisartan treatment significantly attenuated the increased ratio of heart weight to body weight in diabetic rats. The levels of plasma and myocardial adiponectin and the expression of myocardial adipoR1 in diabetic rats were upregulated by telmisartan. Subsequently, the levels of myocardial phospho-AMPK-alpha (Thr172) and the expression of myocardial GLUT4 in diabetic rats were increased by telmisartan. Consequently, the heart function was improved in diabetic rats treated with telmisartan. Conclusions These results suggest that the levels of myocardial adiponectin and its receptor 1 are decreased in type 2 diabetic rats. Telmisartan treatment up-regulates the levels of myocardial adiponectin and its receptor 1, resulting in the increase in myocardial phospho-AMPK-alpha (Thr172) and GLUT4 expression, which may contribute to the improvement of heart function and the decrease in cardiac hypertrophy in diabetic rats.

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