骨骼肌线粒体作为治疗胰岛素抵抗靶点的研究进展

Skeletal muscle mitochondria as a target to treat insulin resistance

IR是肥胖、T2DM发生的共同病理生理机制。骨骼肌是胰岛素介导的葡萄糖摄取、代谢、利用的主要靶器官之一,是IR发生最早和最重要的部位。研究表明,骨骼肌线粒体氧化磷酸化、脂肪酸β氧化、氧化应激以及融合裂变等功能的改变可导致线粒体功能障碍。骨骼肌线粒体功能障碍与IR密切相关,其可能参与了骨骼肌IR的发生发展。本文探讨骨骼肌线粒体功能障碍与IR的关系,并提出以骨骼肌线粒体为靶点,进行运动干预、热量限制、补充抗氧化剂可改善IR,为预防或治疗IR、T2DM提供新思路和方向。

Insulin resistance（IR）is a common pathophysiological mechanism of obesity and type 2 diabetes mellitus（T2DM）.Skeletal muscle is one of the major target organs of insulin-mediated glucose uptake,metabolism and utilization,and it is the earliest and most important site of IR.Studies have shown that the changes of skeletal muscle mitochondrial oxidative phosphorylation,fatty acid beta oxidation,oxidative stress,fusion and fission can lead to mitochondrial dysfunction.Skeletal muscle mitochondrial dysfunction is closely related to IR,which may be involved in the occurrence and development of skeletal muscle IR.Here,we explored the relationship between skeletal muscle mitochondrial dysfunction and IR,and provide various approaches（exercise intervention,calorie restriction,supplement antioxidantsthat affect mitochondrial oxidative metabolism and insulin action and more direct alterations of mitochondrial oxidative metabolism）aimed at improving IR.This will provide new insights and directions for the prevention or treatment of IR and T2DM.