Arsenic Induces Insulin Resistance in Mouse Adipocytes and Myotubes Via Oxidative Stress-Regulated Mitochondrial Sirt3-FOXO3a Signaling Pathway
作者： Sasidharan Padmaja Divya , Poyil Pratheeshkumar , Young-Ok Son , Ram Vinod Roy , John Andrew Hitron
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摘要: Chronic exposure to arsenic via drinking water is associated with an increased risk for development of type 2 diabetes mellitus (T2DM). This study investigates the role mitochondrial oxidative stress protein Sirtuin 3 (Sirt3) and its targeting proteins in chronic arsenic-induced T2DM mouse adipocytes myotubes. The results show that significantly decreased insulin-stimulated glucose uptake (ISGU) correlation reduced expression insulin-regulated transporter 4 (Glut4). Expression Sirt3, a deacetylase, was dramatically along transcription factor, forkhead box O3 (FOXO3a) upon exposure. A decrease membrane potential (Dwm) observed both 3T3L1 C2C12 myotubes treated by arsenic. Reduced FOXO3a activity exhibited binding affinity promoters manganese superoxide dismutase (MnSOD) peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1a, broad powerful regulator reactive oxygen species (ROS) metabolism. Forced Sirt3 or MnSOD elevated Dwm restored ISGU inhibited Our suggest Sirt3/FOXO3a/MnSOD signaling plays significant inhibition induced
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