Department of Occupational and Environment Health, Dalian Medical University, 9 W Lvshun South Road, Dalian, 116044, PR China; Global Health Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian, 116044, PR China. Electronic address: [Email]
Long-term and low-dose exposure to inorganic arsenic is associated with type 2 diabetes (T2D). In this study, C57BL/6 mice exposed to As2O3 showed impaired glucose tolerance, decrease in insulin sensitivity and insulin resistance were observed in the skeletal muscle and myotubes of mice that underwent As2O3 treatment. Decreased insulin-stimulated glucose uptake (ISGU) was also shown by the As2O3-treated myotubes. Moreover, the accumulation of ectopic fat in mice skeletal muscle and myotubes was observed after As2O3 treatment. The upregulated expression of autophagy-associated proteins and the increased number of acidic vesicular organelles (AVOs) indicated that autophagy was stimulated in the skeletal muscle and myotubes of mice after undergoing As2O3 treatment. TAU could prevent the effect of As2O3 on mice skeletal muscle and myotubes, as mentioned above. The impaired ISGU, decreased insulin-associated proteins expression, and increased TAG content caused by As2O3 were reversed by N-acetylcysteine (NAC) and 3-methyladenine (3-MA), and the As2O3-induced autophagy was inhibited by NAC, indicating involvement of ROS-autophagy pathway in the mechanism of As2O3-induced IR and lipid metabolism disorder. In summary, TAU protect against the As2O3-induced IR and ectopic fat accumulation in mice skeletal muscle and myotubes via ROS-autophagy pathway.