脂质超负荷心肌胰岛素抵抗及其防治策略

Strategies for preventing and curing insulin resistance in lipid-overloaded cardiac myocytes

胰岛素抵抗（insulin resistance,IR）是2型糖尿病（type 2 diabetes mellitus,T2DM）最基本也是最重要的病理机制,常出现在T2DM之前,并贯穿于整个病程始终。糖尿病心肌病是T2DM的常见并发症,也是引起心力衰竭,导致60-75%T2DM患者死亡或残废的主要原因[1]。从糖尿病到心力衰竭的分子机制比较复杂，包括血管内皮功能紊乱、糖基化终产物沉积、动脉硬化和冠状动脉病变等。而心肌IR是诱导心脏功能障碍的主要因素。研究发现，

Insulin resistance is a central pathological mechanism of type 2 diabetes mellitus.Diabetic cardiomyopathy and heart failure are frequent co-morbid conditions in type 2 diabetic patients.Long-chain fatty acids（LCFAs） are the major energy source for the heart to sustain contractile activity,and the diabetic heart becomes almost entirely dependent on LCFAs for energy production.Elevated intracellular levels and prolonged accumulation of LCFA metabolites worsen the state of insulin resistance,and further induce diabetic cardiomyopathy and heart failure.It is indicated that sarcolemmal fatty acid uptake and mitochondrial β-oxidation are the rate-limiting steps in cardiac LCFA flux and utilization.Therefore,the inhibitions of carnitine palmitoyltransferase（CPT-I）,β-oxidation enzymes and CD36/plasma membrane fatty acid-binding protein（FABPpm） translocation are the preferable strategies of limiting LCFA entry and LCFA metabolite accumulation,thus regressing cardiac insulin resistance,and eventually preventing diabetic heart failure.