Yang Xiaoping, Zou Duobing, Tang Songtao, Fan Tingting, Su Huan, Hu Ruolei, Zhou Qing, Gui Shuyu, Zuo Li, Wang Yuan
Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
Mol Cell Biochem. 2016 May;416(1-2):23-32. doi: 10.1007/s11010-016-2691-4. Epub 2016 Mar 29.
The increased intestinal permeability and functional impairment play an important role in type 2 diabetes (T2D), and melatonin may possess enteroprotection properties. Therefore, we used streptozotocin-induced diabetic rat model to investigate the regulation of intestinal permeability by melatonin. Rats were randomly divided into three groups, including control, diabetes mellitus (DM), and DM rats treated with melatonin. Melatonin was administered (10 mg/kg/day) by gavage for 24 weeks. The DM rats significantly increased the serum fasting blood glucose and lipid levels, which were alleviated by melatonin treatment. Importantly, the intestinal epithelial permeability was significantly increased in DM rats but was ameliorated following treatment with melatonin. These findings also indicated the expression of myosin light chain kinase (MLCK) and phosphorylation of MLC targeting subunit (MYPT) induced myosin light chain (MLC) phosphorylation level was markedly elevated in hyperglycemic and hyperlipidemic status. They were partly associated with down-regulated membrane type 1 and 2 (MT1 and MT2) expression, and up-regulated Rho-associated protein kinase (ROCK) expression and increased extracellular signal-regulated kinase (ERK) phosphorylation. However, the changes in target protein expression were reversed by melatonin. In conclusion, our results show melatonin beneficial effects on impaired intestinal epithelial permeability in T2D by suppressing ERK/MLCK- and ROCK/MCLP-dependent MLC phosphorylation.
肠道通透性增加和功能损害在2型糖尿病（T2D）中起重要作用，而褪黑素可能具有肠保护特性。因此，我们使用链脲佐菌素诱导的糖尿病大鼠模型来研究褪黑素对肠道通透性的调节作用。大鼠被随机分为三组，包括对照组、糖尿病组（DM）和褪黑素治疗的DM大鼠。通过灌胃给予褪黑素（10 mg/kg/天），持续24周。DM大鼠的血清空腹血糖和血脂水平显著升高，而褪黑素治疗可使其得到缓解。重要的是，DM大鼠的肠上皮通透性显著增加，但褪黑素治疗后有所改善。这些发现还表明，在高血糖和高血脂状态下，肌球蛋白轻链激酶（MLCK）的表达以及靶向亚基（MYPT）的磷酸化诱导的肌球蛋白轻链（MLC）磷酸化水平显著升高。它们部分与膜型1和2（MT1和MT2）表达下调、Rho相关蛋白激酶（ROCK）表达上调以及细胞外信号调节激酶（ERK）磷酸化增加有关。然而，褪黑素可逆转靶蛋白表达的变化。总之，我们的结果表明，褪黑素通过抑制ERK/MLCK和ROCK/MCLP依赖性MLC磷酸化，对T2D中受损的肠上皮通透性具有有益作用。
