Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
Trends Endocrinol Metab. 2010 Feb;21(2):83-8. doi: 10.1016/j.tem.2009.09.008. Epub 2009 Oct 23.
Reactive oxygen species (ROS) are postulated to be a common trigger of insulin resistance. For example, treatment of adipocytes with either tumor-necrosis factor-alpha or dexamethasone increases ROS before impairing glucose uptake. Similarly, treatment with mitochondria-specific antioxidants preserves insulin sensitivity in animal models of insulin resistance. However, it remains unclear whether ROS contribute to insulin resistance in humans. First-degree relatives (FDRs) of type 2 diabetes subjects are at increased risk of developing insulin resistance and type 2 diabetes. Here we review the documented metabolic impairments in FDRs that could contribute to insulin resistance via increased oxidative stress. We propose that lipotoxic intermediates and lipid peroxides in skeletal muscle interfere with insulin signaling and might cause insulin resistance in these 'at risk' individuals.
活性氧（ROS）被认为是胰岛素抵抗的常见触发因素。例如，用肿瘤坏死因子-α或地塞米松处理脂肪细胞会在损害葡萄糖摄取之前增加 ROS。同样，用线粒体特异性抗氧化剂治疗可以在胰岛素抵抗的动物模型中保持胰岛素敏感性。然而，ROS 是否会导致人类的胰岛素抵抗尚不清楚。2 型糖尿病患者的一级亲属（FDRs）发生胰岛素抵抗和 2 型糖尿病的风险增加。在这里，我们回顾了 FDRs 中已记录的代谢损伤，这些损伤可能通过增加氧化应激导致胰岛素抵抗。我们提出，骨骼肌中的脂毒性中间产物和脂质过氧化物会干扰胰岛素信号，并且可能导致这些“高危”个体发生胰岛素抵抗。
