Author:
Wang Chen-Dong,Teng Bao-Song,He Yan-Ming,Wu Jia-Sheng,Pan Deng,Pan Luan-Feng,Zhang Dan,Fan Zhao-Hua,Yang Hong-Jie,Zhou Ping
Abstract
Protein tyrosine phosphatase 1B (PTP1B) is implicated in the negative regulation of the insulin signalling pathway by dephosphorylating the insulin receptor (IR) and IR substrates.Ganodermalucidumhas traditionally been used for the treatment of diabetes in Chinese medicine; however, its anti-diabetic potency and mechanismin vivois still unclear. Our previously published study reported a novel proteoglycan PTP1B inhibitor, named Fudan-Yueyang-Ganoderma lucidum(FYGL) fromG. lucidum, with a half-maximal inhibitory concentration (IC50) value of 5·12 (sem0·05) μg/ml, a protein:polyglycan ratio of 17:77 and 78 % glucose in polysaccharide, and dominant amino acid residues of aspartic acid, glycine, glutamic acid, alanine, serine and threonine in protein.FYGLis capable of decreasing plasma glucose in streptozotocin-induced diabetic mice with a high safety of median lethal dose (LD50) of 6 g/kg. In the present study, C57BL/6db/dbdiabetic mice were trialed further usingFYGLas well as metformin for comparison. Oral treatment withFYGLindb/dbdiabetic mice for 4 weeks significantly (P < 0·01 or 0·05) decreased the fasting plasma glucose level, serum insulin concentration and the homeostasis model assessment of insulin resistance.FYGLalso controlled the biochemistry indices relative to type 2 diabetes-accompanied lipidaemic disorders. Pharmacology research suggests thatFYGLdecreases the plasma glucose level by the mechanism of inhibiting PTP1B expression and activity, consequently, regulating the tyrosine phosphorylation level of the IR β-subunit and the level of hepatic glycogen, thus resulting in the improvement of insulin sensitivity. Therefore,FYGLis promising as an insulin sensitiser for the therapy of type 2 diabetes and accompanied dyslipidaemia.
Publisher
Cambridge University Press (CUP)
Subject
Nutrition and Dietetics,Medicine (miscellaneous)
Cited by
41 articles.
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