Chronic insulin treatment causes insulin resistance in 3T3-L1 adipocytes through oxidative stress
Chronic insulin treatment causes insulin resistance in 3T3-L1 adipocytes through oxidative stress
复制标题
长期胰岛素治疗通过氧化应激导致 3T3-L1 脂肪细胞胰岛素抵抗
DOI：
10.1080/10715760802158448
复制
发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Zhai, Qiwei
中科院分区：
文献类型：
--
作者：
Ge, Xuemei;Yu, Qiujing;Zhai, Qiwei
胰岛素抵抗和高胰岛素血症常见于肥胖和糖尿病前期，高胰岛素血症既是胰岛素抵抗的标志物，也是胰岛素抵抗的原因。然而，高胰岛素血症和胰岛素抵抗之间的分子联系仍然难以捉摸。本研究检测了慢性胰岛素处理对3 T3-L1脂肪细胞活性氧（ROS）产生、胰岛素信号传导和胰岛素刺激的葡萄糖摄取的影响。结果表明，慢性胰岛素处理显著增加细胞内超氧阴离子、过氧化氢和羟自由基的产生。慢性胰岛素处理诱导的ROS抑制胰岛素信号传导和葡萄糖摄取，诱导内质网（ER）应激和JNK激活。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上述效应。这些结果提示ROS、ER应激和JNK通路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潜在干预靶点。
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.