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Chromium (VI) induces insulin resistance in 3T3-L1 adipocytes through elevated reactive oxygen species generation
Authors:Xuemei Ge  Zhen Liu  Wei Qi  Xianglin Shi
Institution: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, 200031, PR China
Abstract: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.
Keywords:Cr(VI)  insulin resistance  ROS  ER stress  JNK
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