Zinc is an essential trace element that is often reduced under the type 1 diabetic condition. Previous studies demonstrated that zinc deficiency enhanced type 1 diabetes-induced liver injury and that zinc supplementation significantly helped to prevent this. Due to the differences in pathogenesis between type 1 and type 2 diabetes, it is unknown whether zinc supplementation can induce a beneficial effect on type 2 diabetes-induced liver injury. This possible protective mechanism was investigated in the present study. A high-fat diet, along with a one-time dose of streptozotocin, was applied to metallothionein (MT) knockout mice, nuclear factor-erythroid 2-related factor (Nrf) 2 knockout mice, and age-matched wild-type (WT) control mice, in order to induce type 2 diabetes. This was followed by zinc treatment at 5 mg/kg body weight given every other day for 3 months. Global metabolic disorders of both glucose and lipids were unaffected by zinc supplementation. This induced preventive effects on conditions caused by type 2 diabetes like oxidative stress, apoptosis, the subsequent hepatic inflammatory response, fibrosis, hypertrophy, and hepatic dysfunction. Additionally, we also observed that type 2 diabetes reduced hepatic MT expression, while zinc supplementation induced hepatic MT expression. This is a crucial antioxidant. A mechanistic study showed that MT deficiency blocked zinc supplementation-induced hepatic protection under the condition of type 2 diabetes. This suggested that endogenous MT is involved in the hepatic protection of zinc supplementation in type 2 diabetic mice. Furthermore, zinc supplementation-induced hepatic MT increase was unobserved once Nrf2 was deficient, indicating that Nrf2 mediated the upregulation of hepatic MT in response to zinc supplementation. Results of this study indicated that zinc supplementation prevented type 2 diabetes-induced liver injury through the activation of the Nrf2-MT-mediated antioxidative pathway.

中文翻译：

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锌补充剂可预防 Nrf2-MT 抗氧化途径介导的 2 型糖尿病引起的肝损伤

锌是一种必需的微量元素，在 1 型糖尿病情况下通常会减少。先前的研究表明，缺锌会加重 1 型糖尿病引起的肝损伤，而补锌显着有助于预防这种情况。由于 1 型和 2 型糖尿病的发病机制不同，尚不清楚补锌是否可以对 2 型糖尿病引起的肝损伤产生有益作用。在本研究中研究了这种可能的保护机制。对金属硫蛋白 (MT) 敲除小鼠、核因子-红细胞 2 相关因子 (Nrf) 2 敲除小鼠和年龄匹配的野生型 (WT ) 对照小鼠，以诱导 2 型糖尿病。随后每隔一天给予 5 mg/kg 体重的锌治疗，持续 3 个月。葡萄糖和脂质的全球代谢紊乱不受锌补充剂的影响。这对由 2 型糖尿病引起的疾病（如氧化应激、细胞凋亡、随后的肝脏炎症反应、纤维化、肥大和肝功能障碍）产生了预防作用。此外，我们还观察到 2 型糖尿病降低了肝脏 MT 的表达，而补锌诱导了肝脏 MT 的表达。这是一种重要的抗氧化剂。一项机制研究表明，在 2 型糖尿病的情况下，MT 缺乏会阻断锌补充剂诱导的肝脏保护。这表明内源性 MT 参与了 2 型糖尿病小鼠补锌的肝保护。此外，一旦 Nrf2 缺乏，补锌诱导的肝脏 MT 增加就没有观察到，这表明 Nrf2 介导了对补锌的肝脏 MT 上调。这项研究的结果表明，锌补充剂通过激活 Nrf2-MT 介导的抗氧化途径来预防 2 型糖尿病引起的肝损伤。