Sreekumar Raghavakaimal, Nair K Sreekumaran
Endocrinology Division, Mayo Clinic, Rochester, MN 55905, USA.
Indian J Med Res. 2007 Mar;125(3):399-410.
Skeletal muscle insulin resistance is a key contributor to the pathophysiology of type 2 diabetes. Recent studies have shown that insulin resistance in a variety of conditions including type 2 diabetes, ageing and in offspring of type 2 diabetes is associated with muscle mitochondrial dysfunction. The important question is whether insulin resistance results from muscle mitochondrial dysfunction or vise versa. Gene array studies from muscle biopsy samples showed that transcript levels of several genes, especially OXPHOS genes are altered in type 2 diabetic patients during poor glycaemic control but many of these alterations are normalized by insulin treatment suggesting that reduced insulin action is a factor involved in muscle mitochondrial dysfunction. Moreover, insulin infusion while maintaining glucose and amino acid levels results in increase in muscle mitochondrial gene transcript levels and ATP production indicating that insulin is a key regulator of muscle mitochondrial biogenesis. At a similar post-absorptive insulin levels both type 2 diabetic patients and non diabetic controls have similar muscle mitochondrial ATP production but increasing insulin from low to high levels stimulate ATP production only in non diabetic people but not in the diabetic people. The lack of muscle mitochondrial response to insulin in type 2 diabetic patients is likely to be related to insulin resistance and reduced substrate utilization.
骨骼肌胰岛素抵抗是2型糖尿病病理生理学的关键因素。最近的研究表明，在包括2型糖尿病、衰老以及2型糖尿病患者后代等多种情况下的胰岛素抵抗都与肌肉线粒体功能障碍有关。重要的问题是胰岛素抵抗是由肌肉线粒体功能障碍导致的，还是反之亦然。对肌肉活检样本进行的基因阵列研究表明，在血糖控制不佳的2型糖尿病患者中，几个基因的转录水平，尤其是氧化磷酸化基因的转录水平发生了改变，但其中许多改变通过胰岛素治疗得以恢复正常，这表明胰岛素作用减弱是肌肉线粒体功能障碍的一个相关因素。此外，在维持血糖和氨基酸水平的同时输注胰岛素会导致肌肉线粒体基因转录水平和ATP生成增加，这表明胰岛素是肌肉线粒体生物合成的关键调节因子。在相似的吸收后胰岛素水平下，2型糖尿病患者和非糖尿病对照者的肌肉线粒体ATP生成相似，但将胰岛素水平从低提高到高时，仅能刺激非糖尿病患者的ATP生成，而不能刺激糖尿病患者的ATP生成。2型糖尿病患者肌肉线粒体对胰岛素缺乏反应可能与胰岛素抵抗和底物利用减少有关。
