Dumas J-F, Simard G, Flamment M, Ducluzeau P-H, Ritz P
Inserm U694, 49033 Angers, France.
Diabetes Metab. 2009 Jun;35(3):159-67. doi: 10.1016/j.diabet.2009.02.002. Epub 2009 Apr 5.
The precise cause of insulin resistance and type 2 diabetes is unknown. However, there is a strong association between insulin resistance and lipid accumulation - and, in particular, lipotoxic fatty acid metabolites - in insulin-target tissues. Such accumulation is known to cause insulin resistance, particularly in skeletal muscle, by reducing insulin-stimulated glucose uptake. Reduced fat-oxidation capacity appears to cause such lipid accumulation and, over the past few years, many studies have concluded that decreased mitochondrial oxidative phosphorylation could be the initiating cause of lipid deposition and the development of insulin resistance. The aim of this review is to summarize the latest findings regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance in humans. At present, there are too few studies to definitively conclude that, in this context, mitochondria are functionally impaired (dysfunction in the respiratory chain). Indeed, insulin resistance could also be related to a decrease in the number of mitochondria or to a combination of this and mitochondrial dysfunction. Finally, we also consider whether or not these aberrations could be the cause of the development of the disease or whether mitochondrial dysfunction may simply be the consequence of an insulin-resistant state.
胰岛素抵抗和2型糖尿病的确切病因尚不清楚。然而，在胰岛素靶组织中，胰岛素抵抗与脂质蓄积，尤其是脂毒性脂肪酸代谢产物之间存在密切关联。已知这种蓄积会通过减少胰岛素刺激的葡萄糖摄取导致胰岛素抵抗，尤其是在骨骼肌中。脂肪氧化能力降低似乎会导致这种脂质蓄积，在过去几年中，许多研究得出结论，线粒体氧化磷酸化降低可能是脂质沉积和胰岛素抵抗发展的起始原因。本综述的目的是总结关于人类骨骼肌线粒体功能障碍与胰岛素抵抗之间联系的最新研究结果。目前，研究数量过少，无法明确得出在这种情况下线粒体功能受损（呼吸链功能障碍）的结论。事实上，胰岛素抵抗也可能与线粒体数量减少或这两者与线粒体功能障碍的组合有关。最后，我们还考虑这些异常是否可能是疾病发展的原因，或者线粒体功能障碍是否可能仅仅是胰岛素抵抗状态的结果。
