Taurine protects against arsenic trioxide-induced insulin resistance via ROS-Autophagy pathway in skeletal muscle

Abstract

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.

Keywords: Arsenic; Autophagy; Insulin resistance; Skeletal muscle; Taurine.