Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal (perirenal, perigonadal, and omentum) and subcutaneous lumbar white adipose tissues (IWAT and SWAT, respectively). Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight/day) or vehicle for 6 weeks. Zn and Cu concentrations were not significantly influenced by diabesity in the analyzed tissues (p > 0.05), with the exception of Zn in liver. In skeletal muscle Zn and Cu, and in perirenal WAT, only Zn levels increased significantly with melatonin supplementation in ZDF rats (p < 0.05). This cytoplasmic Zn enhancement would be probably associated with the upregulation of several Zn influx membrane transporters (Zips) and could explain the amelioration in the glycaemia and insulinaemia by upregulating the Akt and downregulating the inhibitor PTP1B, in obese and diabetic conditions. Enhanced Zn and Cu levels in muscle cells could be related to the reported antioxidant melatonin activity exerted by increasing the Zn, Cu-SOD, and extracellular Cu-SOD activity. In conclusion, melatonin, by increasing the muscle levels of Zn and Cu, joined with our previously reported findings improves glycaemia, insulinaemia, and oxidative stress in this diabesity animal model.

中文翻译：

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褪黑激素改善糖尿病肥胖大鼠肌肉中锌和铜的含量

褪黑激素改善与肥胖及其糖尿病（糖尿病）相关的代谢改变。我们打算通过改变肝脏、肌肉、胰腺和大脑以及内部（肾周、性腺和大网膜）和皮下腰部白色脂肪组织（IWAT 和 SWAT，分别）。雄性 Zücker 糖尿病脂肪 (ZDF) 大鼠和瘦同窝仔 (ZL) 口服补充褪黑激素 (10 毫克/公斤体重/天) 或载体 6 周。除了肝脏中的锌外，锌和铜的浓度不受所分析组织中糖尿病的显着影响（p > 0.05）。在骨骼肌 Zn 和 Cu 以及肾周 WAT 中，ZDF 大鼠中只有 Zn 水平随着褪黑激素的补充而显着增加（p< 0.05)。这种细胞质 Zn 增强可能与几种 Zn 流入膜转运蛋白 (Zips) 的上调有关，并且可以解释在肥胖和糖尿病条件下通过上调 Akt 和下调抑制剂 PTP1B 来改善血糖和胰岛素血症。肌肉细胞中 Zn 和 Cu 水平的提高可能与报道的抗氧化褪黑激素活性有关，该活性通过增加 Zn、Cu-SOD 和细胞外 Cu-SOD 活性而发挥作用。总之，褪黑激素通过增加肌肉中锌和铜的水平，与我们之前报道的研究结果相结合，在这种糖尿病动物模型中改善了血糖、胰岛素血症和氧化应激。