Type 2 diabetes mellitus (T2D) is a metabolic disorder caused by chronic hyperglycemia due to a deficiency in the secretion and/or action of insulin. Zinc (Zn) supplementation and strength exercise increases insulin signaling. We evaluate the effect of Zn supplementation and strength exercise on insulin resistance in the liver of rats with diet-induced T2D through the study of phosphorylation of Akt and protein tyrosine phosphatase 1B (PTP1B). Rats were fed with a high-fat diet (HFD) for 18 weeks to induce T2D and then assigned in four experimental groups: HFD, HFD-Zn (Zn), HFD-strength exercise (Ex), and HFD-Zn/strength exercise (ZnEx) and treated during 12 weeks. Serum Zn, lipid profile, transaminases, glucose, and insulin were measured. In the liver with/without insulin stimuli, total and phosphorylated Akt (pAkt^Ser473) and PTP1B (pPTP1B^Ser50) were determined by western blot. Hepatic steatosis was evaluated by histological staining with red oil and intrahepatic triglyceride (IHTG) content. There were no differences in biochemical and body-related variables. The ZnEx group showed a higher level of pAkt, both with/without insulin. The ZnEx group also showed higher levels of pPTP1B with respect to HFD and Zn groups. The ZnEx group had higher levels of pPTP1B than groups treated with insulin. Liver histology showed a better integrity and less IHTG in Ex and ZnEx with respect to the HFD group. The Ex and ZnEx groups had lower IHTG with respect to the HFD group. Our results showed that Zn supplementation and strength exercise together improved insulin signaling and attenuated nonalcoholic liver disease in a T2D rat model.

2 型糖尿病 (T2D) 是一种由胰岛素分泌和/或作用不足引起的慢性高血糖症引起的代谢紊乱。锌 (Zn) 补充剂和力量锻炼可增加胰岛素信号传导。我们通过研究 Akt 和蛋白酪氨酸磷酸酶 1B (PTP1B) 的磷酸化来评估补锌和力量运动对饮食诱导的 T2D 大鼠肝脏胰岛素抵抗的影响。给大鼠喂食高脂饮食 (HFD) 18 周以诱发 T2D，然后分配到四个实验组：HFD、HFD-Zn (Zn)、HFD 强度运动 (Ex) 和 HFD-Zn/强度运动(ZnEx) 并在 12 周内进行治疗。测量了血清锌、脂质谱、转氨酶、葡萄糖和胰岛素。在有/无胰岛素刺激的肝脏中，总 Akt 和磷酸化 Akt（pAkt ^Ser473) 和 PTP1B (pPTP1B ^Ser50 ) 通过蛋白质印迹测定。通过用红油和肝内甘油三酯 (IHTG) 含量进行组织学染色来评估肝脂肪变性。生化和身体相关变量没有差异。ZnEx 组显示出更高水平的 pAkt，无论是否使用胰岛素。相对于 HFD 和 Zn 组，ZnEx 组也显示出更高水平的 pPTP1B。ZnEx 组的 pPTP1B 水平高于胰岛素治疗组。与 HFD 组相比，Ex 和 ZnEx 的肝组织学显示出更好的完整性和更少的 IHTG。Ex 和 ZnEx 组相对于 HFD 组具有较低的 IHTG。我们的研究结果表明，在 T2D 大鼠模型中，锌补充剂和力量锻炼共同改善了胰岛素信号传导并减轻了非酒精性肝病。