On the expression of cardiac adiponectin and its receptor 1 by telmisartan tn diabetic rats

Abstract

Objective To observe the effects of telmisartan on the expression of cardiac adiponectin and its receptor 1 in diabetic rats.and to investigate the protective roles and mechanisms of telmisartan on cardiomyopathy of diabetic rats.Methods Thirty male Wistar rats were randomly divided inlo control group.diabetic group,and telmisartan group.Diabetes mellitus was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin.After establishment of diabetes model.telmisartan(5 mg·kg~(-1)·d~(-1))was administered by lavage for 12 weeks in telmisartan group.At termination,the cardiac function was detected.Plasma and myocardial adiponectin levels were assayed by enzyme immunoassay.mRNA expression of adiponectin receptor 1(adipoR1)was assayed by RT-PCR,and protein expression of adipoR1,phosphorylated-AMPK-α,and glucose transporter 4(GluT4)were determined by Western blotting in myocardium.Results After12 weeks,the ratio of heart to body weight was increased[(4.38±0.07 vs 2.99±0.67)g/kg,P<0.05],but adiponectin levels in plasma and myocardium were decreased[(1.09±0.03 vs 1.87±0.05)μg/ml,(0.12±0.02vs 0.21±0.02)μg/mg protein,both P<0.05]in diabetic rats.In myocardium of diabetic rats,the protein and mRNA of adipoR1 were also decreased(0.35±0.08 vs 0.78±0.11,0.34±0.07 vs 0.77±0.08,both P<0.05).so were the expressions of phosphorylated-AMPK-α and GluT_4(0.47±0.12 vs 0.72±0.10,0.41±0.09 vs 0.79±0.08.both P<0.05).The cardiac function was also significantly decreased in diabetic group.The ratio of heart to body weight was significantly decreased in telmisartan group[(3.49±0.39 vs 4.38±0.07)g/kg,P<0.05].Both of plasma and myocardial adiponectin levels were increased[(1.4±0.02 vs 1.09±0.03)μg/ml,(0.16±0.01 vs 0.12±0.02)μg/mg protein,P<0.05],as well as mRNA(0.48±0.06 vs 0.35±0.08)and protein expression of adipoR1(0.47±0.09 vs 0.34±0.07),phosphorylated-AMPK-α(0.57±0.10 vs 0.47±0.12),and GluT_4(0.52±0.10 vs 0.41 ±0.09,all P<0.05)in myocardium.The cardiac function was obviously improved after telmisartan treatment(P < 0.05).Conclusion The levels of myocardial adiponectin and its receptor 1 are decreased in diabetic rats.Telmisartan up-regulates the levels of myocardial adiponectin and its receptor 1 and may promote myocardial glucose oxidation,resulting in the improvement of heart function in diabetic rats. Key words: Telmisartan; Diabetes mellitus,experimental; Adiponectin receptor 1 ; Cardiomyopathy