Chromium (VI) induces insulin resistance in 3T3-L1 adipocytes through elevated reactive oxygen species generation.
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.
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.
Xuemei
X
Ge
Zhen
Z
Liu
Wei
W
Qi
Xianglin
X
Shi
Qiwei
Q
Zhai
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D000838:Anions; D002454:Cell Differentiation; D002857:Chromium / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007333:Insulin Resistance; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism
D000838:Anions; D017382:Reactive Oxygen Species; D002857:Chromium; D013481:Superoxides; D006861:Hydrogen Peroxide; D048670:MAP Kinase Kinase 4; D005947:Glucose