Department of Occupational and Environment Health, Dalian Medical University, 9 W Lvshun South Road, Dalian, 116044, PR China.
Experimental Teaching Center of Public Health, Dalian Medical University, 9 W Lvshun South Road, Dalian, 116044, PR China.
Int J Biochem Cell Biol. 2019 Jul;112:50-60. doi: 10.1016/j.biocel.2019.05.001. Epub 2019 May 3.
Long-term and low-dose exposure to inorganic arsenic is associated with type 2 diabetes (T2D). In this study, C57BL/6 mice exposed to AsO showed impaired glucose tolerance, decrease in insulin sensitivity and insulin resistance were observed in the skeletal muscle and myotubes of mice that underwent AsO treatment. Decreased insulin-stimulated glucose uptake (ISGU) was also shown by the AsO-treated myotubes. Moreover, the accumulation of ectopic fat in mice skeletal muscle and myotubes was observed after AsO 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 AsO treatment. TAU could prevent the effect of AsO on mice skeletal muscle and myotubes, as mentioned above. The impaired ISGU, decreased insulin-associated proteins expression, and increased TAG content caused by AsO were reversed by N-acetylcysteine (NAC) and 3-methyladenine (3-MA), and the AsO-induced autophagy was inhibited by NAC, indicating involvement of ROS-autophagy pathway in the mechanism of AsO-induced IR and lipid metabolism disorder. In summary, TAU protect against the AsO-induced IR and ectopic fat accumulation in mice skeletal muscle and myotubes via ROS-autophagy pathway.
长期低剂量接触无机砷与 2 型糖尿病（T2D）有关。在这项研究中，暴露于砷酸盐的 C57BL/6 小鼠表现出葡萄糖耐量受损，接受砷酸盐治疗的小鼠骨骼肌和肌管中胰岛素敏感性降低和胰岛素抵抗。砷酸盐处理的肌管也表现出胰岛素刺激的葡萄糖摄取（ISGU）减少。此外，在接受砷酸盐治疗后，小鼠骨骼肌和肌管中观察到异位脂肪的积累。自噬相关蛋白的上调和酸性囊泡细胞器（AVOs）的增加表明，在接受砷酸盐治疗后，小鼠骨骼肌和肌管中的自噬被激活。如前所述，TAU 可以预防砷酸盐对小鼠骨骼肌和肌管的影响。N-乙酰半胱氨酸（NAC）和 3-甲基腺嘌呤（3-MA）逆转了砷酸盐引起的 ISGU 受损、胰岛素相关蛋白表达减少和 TAG 含量增加，NAC 抑制了砷酸盐诱导的自噬，表明 ROS-自噬通路参与了砷酸盐诱导的 IR 和脂质代谢紊乱的机制。总之，TAU 通过 ROS-自噬通路来防止砷酸盐引起的小鼠骨骼肌和肌管中的 IR 和异位脂肪积累。
