title: Ameliorative effect of melatonin against increased intestinal permeability in diabetic rats: possible involvement of MLCK-dependent MLC phosphorylation.
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.
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Duobing
authors.initials: D
authors.lastname: Zou
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Fan
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Su
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.|Key Laboratory of Gene Research of Anhui Province, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Ruolei
authors.initials: R
authors.lastname: Hu
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.|Key Laboratory of Gene Research of Anhui Province, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.|Key Laboratory of Gene Research of Anhui Province, Hefei, 230032, Anhui, People's Republic of China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Gui
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China. lizuo1981@163.com.|Key Laboratory of Gene Research of Anhui Province, Hefei, 230032, Anhui, People's Republic of China. lizuo1981@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China. aydesm-1@163.com.|Key Laboratory of Gene Research of Anhui Province, Hefei, 230032, Anhui, People's Republic of China. aydesm-1@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000493:pharmacokinetics* / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D018994:Myosin Light Chains; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D008550:Melatonin
keywords: Diabetes; Intestinal epithelial permeability; Melatonin; Myosin light chain kinase