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Ameliorative effect of melatonin against increased intestinal permeability in diabetic rats: possible involvement of MLCK-dependent MLC phosphorylation

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Abstract

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.

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Acknowledgments

This study was supported by the National Nature Science Research Grants (Nos.: 81272399, 81470568), Fund of colleges excellent young key projects in Anhui Province (No. 2013SQRL101ZD), and the Anhui Natural Science Foundation (No. 1508085QH167), Doctor fund of Anhui Medical University (No. 0108020103).

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    Authors and Affiliations

    1. Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China

      Xiaoping Yang, Duobing Zou, Huan Su, Ruolei Hu, Qing Zhou, Li Zuo & Yuan Wang

    2. Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China

      Songtao Tang

    3. Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China

      Tingting Fan & Shuyu Gui

    4. Key Laboratory of Gene Research of Anhui Province, Hefei, 230032, Anhui, People’s Republic of China

      Ruolei Hu, Qing Zhou, Shuyu Gui, Li Zuo & Yuan Wang

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    1. Xiaoping Yang
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    Xiaoping Yang, Duobing Zou, and Songtao Tang have contributed equally to this work.

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    Yang, X., Zou, D., Tang, S. et al. Ameliorative effect of melatonin against increased intestinal permeability in diabetic rats: possible involvement of MLCK-dependent MLC phosphorylation. Mol Cell Biochem 416, 23–32 (2016). https://doi.org/10.1007/s11010-016-2691-4

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