Ge Xuemei, Liu Zhen, 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):554-63. doi: 10.1080/10715760802155113.
Reactive oxygen species (ROS) have been proposed to be involved in the development of insulin resistance, although the exact molecular link between ROS and insulin resistance remains to be determined. Chromium (Cr(VI)) is known as an inducer of ROS. Therefore, this study examined whether Cr(VI) could induce insulin resistance. It demonstrated that Cr(VI) treatment significantly inhibited insulin-stimulated glucose uptake and attenuated insulin signalling. Moreover, Cr(VI) treatment markedly increased the intracellular levels of superoxide anion, hydrogen peroxide and hydroxyl radical. N-acetylcysteine, superoxide dismutase and catalase can block the ROS generation and alleviate the insulin resistance induced by Cr(VI) treatment. In addition, Cr(VI) treatment induced endoplasmic reticulum (ER) stress and JNK activation and these effects were diminished by N-acetylcysteine. These results suggested that ROS generation through Cr(VI) treatment cause ER stress, JNK activation and insulin resistance in adipocytes. Therefore, the oxidative stress could be a potential interventional target for insulin-resistance related diseases.
活性氧（ROS）已被认为与胰岛素抵抗的发生有关，尽管ROS与胰岛素抵抗之间的确切分子联系仍有待确定。铬（Cr(VI)）是已知的ROS诱导剂。因此，本研究检测了Cr(VI)是否能诱导胰岛素抵抗。结果表明，Cr(VI)处理显著抑制胰岛素刺激的葡萄糖摄取并减弱胰岛素信号传导。此外，Cr(VI)处理显著增加了细胞内超氧阴离子、过氧化氢和羟基自由基的水平。N-乙酰半胱氨酸、超氧化物歧化酶和过氧化氢酶可阻断ROS生成并减轻Cr(VI)处理诱导的胰岛素抵抗。此外，Cr(VI)处理诱导内质网（ER）应激和JNK激活，而N-乙酰半胱氨酸可减轻这些效应。这些结果表明，Cr(VI)处理产生的ROS导致脂肪细胞中的ER应激、JNK激活和胰岛素抵抗。因此，氧化应激可能是胰岛素抵抗相关疾病的潜在干预靶点。
