Department of Endocrinology, Second Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
J Pharm Pharmacol. 2011 Jan;63(1):87-94. doi: 10.1111/j.2042-7158.2010.01157.x. Epub 2010 Oct 11.
This study investigated the effect of telmisartan on the expression of cardiac adiponectin and its receptor 1 in type 2 diabetic rats.
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)-α, phospho-AMPK-α (Thr172) and glucose transporter 4(GLUT4) was determined by Western blotting.
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-α (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-α (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.
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-α (Thr172) and GLUT4 expression, which may contribute to the improvement of heart function and the decrease in cardiac hypertrophy in diabetic rats.
本研究旨在探讨替米沙坦对 2 型糖尿病大鼠心脏脂联素及其受体 1 表达的影响。
36 只雄性 Wistar 大鼠随机分为对照组（C 组，n = 10）和糖尿病组（n = 26）。采用高脂高糖饮食联合小剂量链脲佐菌素（STZ）腹腔注射诱导 2 型糖尿病。糖尿病诱导后，糖尿病大鼠再次随机分为糖尿病组（D 组，n = 10）和糖尿病治疗组（DT 组，n = 10）。替米沙坦（5 mg/kg/天）灌胃治疗糖尿病治疗组大鼠 12 周。12 周后，检测心功能。酶联免疫吸附试验（ELISA）检测血浆和心肌脂联素水平。逆转录-聚合酶链反应（RT-PCR）检测心肌脂联素受体 1（adipiR1）的 mRNA 表达。Western blot 检测心肌 adipiR1、AMP 激活蛋白激酶（AMPK）-α、磷酸化 AMPK-α（Thr172）和葡萄糖转运蛋白 4（GLUT4）的蛋白表达。
与对照组相比，糖尿病大鼠心脏重量与体重的比值显著增加。糖尿病大鼠血浆和心肌脂联素水平降低，心肌 adipoR1 蛋白和 mRNA 表达降低，导致心肌 AMPK-α（Thr172）磷酸化和 GLUT4 蛋白表达降低，心功能下降。替米沙坦治疗可显著减轻糖尿病大鼠心脏重量与体重的比值增加。替米沙坦治疗可上调糖尿病大鼠血浆和心肌脂联素水平及心肌 adipoR1 表达。随后，替米沙坦可增加糖尿病大鼠心肌磷酸化 AMPK-α（Thr172）和 GLUT4 的表达。因此，替米沙坦可改善糖尿病大鼠的心功能。
这些结果表明，2 型糖尿病大鼠心肌脂联素及其受体 1 水平降低。替米沙坦治疗可上调心肌脂联素及其受体 1 水平，增加心肌磷酸化 AMPK-α（Thr172）和 GLUT4 表达，从而改善心功能，减轻糖尿病大鼠心肌肥厚。
