Ge Xuemei, Yu Qiujing, Qi Wei, Shi Xianglin, Zhai Qiwei
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, PR China.
Free Radic Res. 2008 Jun;42(6):582-91. doi: 10.1080/10715760802158448.
Insulin resistance and hyperinsulinemia are commonly present in obesity and pre-diabetes, and hyperinsulinemia is both a marker and a cause for insulin resistance. However, the molecular link between hyperinsulinemia and insulin resistance remains elusive. The present study examined the effect of chronic insulin treatment on the reactive oxygen species (ROS) production, insulin signalling and insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The results showed that chronic insulin treatment significantly increased the intracellular generation of superoxide anion, hydrogen peroxide and hydroxyl radical. ROS induced by chronic insulin treatment inhibited insulin signalling and glucose uptake, induced endoplasmic reticulum (ER) stress and JNK activation. Furthermore, these effects were reversed by antioxidants N-acetylcysteine, superoxide dismutase or catalase. These results suggested that ROS, ER stress and JNK pathway are involved in insulin resistance induced by chronic insulin treatment. Therefore, oxidative stress could be a potential interventional target for hyperinsulinemia-induced insulin resistance and related diseases.
胰岛素抵抗和高胰岛素血症常见于肥胖症和糖尿病前期，且高胰岛素血症既是胰岛素抵抗的一个标志物，也是其成因。然而，高胰岛素血症与胰岛素抵抗之间的分子联系仍不清楚。本研究检测了慢性胰岛素治疗对3T3-L1脂肪细胞中活性氧（ROS）生成、胰岛素信号传导及胰岛素刺激的葡萄糖摄取的影响。结果显示，慢性胰岛素治疗显著增加了细胞内超氧阴离子、过氧化氢和羟基自由基的生成。慢性胰岛素治疗诱导产生的ROS抑制了胰岛素信号传导和葡萄糖摄取，诱导了内质网（ER）应激和JNK激活。此外，抗氧化剂N-乙酰半胱氨酸、超氧化物歧化酶或过氧化氢酶可逆转这些效应。这些结果表明，ROS、ER应激和JNK途径参与了慢性胰岛素治疗诱导的胰岛素抵抗。因此，氧化应激可能是高胰岛素血症诱导的胰岛素抵抗及相关疾病的一个潜在干预靶点。
