Effect of rosiglitazone on myocardial energy substrate utilization in type 2 diabetic rats |
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| Authors: | WEN Zhong-yuan LIU Yong-ming WANG Teng ZHANG Ping-an CHEN Xiao-lin LI Geng-shan |
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| Institution: | Department of Endocrine People's Hospital, Wuhan University, Wuhan 430060, China |
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| Abstract: | AIM: To study the effect of rosiglitazone (RSG) to improve insulin sensitivity on myocardial energy substrate utilization as well as the cardiac function in a rat model of type 2 diabetes mellitus. METHODS: Sprague-Dawley rats were conducted into three groups: chow-fed rats were fed with normal chow (12% of calories as fat); fat-fed/STZ rats were fed with high-fat diet (40% of calories as fat) for 4 weeks and then injected with streptozotocin 35 mg/kg intraperitoneal; fat-fed/STZ/RSG rats were fat-fed/STZ rats treated with rosiglitazone (3 mg·kg-1·d-1) for 2 weeks. A cannula connected to a passive transducer was inserted the heart for the measurement of the cardiac function including heart rate (HR), left ventricular end-diastolic pressure (EDP) and ±dp/dtmax. Then the isolated hearts were mounted onto a Langendorff perfusion apparatus to perfuse with Krebs-Henseleit buffer in the presence of 5 mmol/L glucose and 0.4 mmol/L ［3H］ labelled palmitate. Glucose uptake and ［3H2O］ collection were measured to evaluate the rate of carbohydrate and fatty acid oxidation. RESULTS: Compared with the chow-fed rats, fat-fed/STZ rats had a significantly depression of glucose uptake in the hearts ［(54.7±6.2 vs 69.0±5.7) μmol·g-1 dry weight, P<0.01］ after 30 min perfusion. The oxidation of glucose and palmitate were 18% and 82%, respectively. Paralleling the reduction was a change of EDP ［(14.3±1.8 vs 10.5±1.1) mmHg, P<0.05］ and -dp/dt ［(550±57 vs 650±42) mmHg/s, P<0.01］, indicating a impaired left ventricular diastolic function. In the hearts subjected to fat-fed/STZ group, rosiglitazone treated for 2 weeks resulted in a elevated level of glucose uptake ［(63.5±6.4 vs 54.7±6.2) μmol·g-1 dry weight, P<0.05］. A protective role of the ventricular function ［EDP decreased from （14.8±1.9） to （11.0±0.8） mmHg/s and -dp/dtmax increased from （558±60） to （629±51） mmHg/s, P<0.05］ were observed. CONCLUSIONS: Our study indicates that there is a depression of glucose oxidation and at increase in fatty acid oxidation in type 2 diabetic hearts. Elevation of insulin sensitivity using rosiglitazone increases the myocardial glucose metabolism and shows a benefitial result to heart functions. |
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