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(-)-表没食子儿茶素没食子酸酯的微生物代谢产物对L6骨骼肌细胞葡萄糖摄取及ICR小鼠葡萄糖耐量的影响

Effects of Microbial Metabolites of (-)-Epigallocatechin Gallate on Glucose Uptake in L6 Skeletal Muscle Cell and Glucose Tolerance in ICR Mice.

作者信息

Takagaki Akiko, Yoshioka Yasukiyo, Yamashita Yoko, Nagano Tomoya, Ikeda Masaki, Hara-Terawaki Aya, Seto Ryota, Ashida Hitoshi

机构信息

Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University.

R&D Group, Mitsui Norin Company, Limited.

出版信息

Biol Pharm Bull. 2019;42(2):212-221. doi: 10.1248/bpb.b18-00612.

Abstract

Glucose uptake ability into L6 skeletal muscle cell was examined with eleven kinds of ring fission metabolites of (-)-epigallocatechin gallate (EGCG) produced by intestinal bacteria. The metabolites 5-(3,5-dihydroxyphenyl)-γ-valerolactone (EGC-M5), 4-hydroxy-5-(3,4,5-trihydroxyphenyl)valeric acid (EGC-M6), 5-(3,4,5-trihydroxyphenyl)-γ-valerolactone (EGC-M7) and 5-(3-hydroxyphenyl)valeric acid (EGC-M11) have been found to promote uptake of glucose into L6 myotubes significantly. EGC-M5, which is one of the major ring fission metabolites of EGCG, was also found to have a promotive effect on glucose transporter 4 (GLUT4) translocation accompanied by phosphorylation of AMP-activated protein kinase (AMPK) signaling pathway in skeletal muscle both in vivo and in vitro. Furthermore, the effect of oral single dosage of EGC-M5 on glucose tolerance test with ICR mice was examined and significant suppression of hyperglycemia was observed. These data suggested that EGC-M5 has an antidiabetic effect in vivo.

摘要

利用肠道细菌产生的11种表没食子儿茶素没食子酸酯(EGCG)的环裂变代谢产物,检测其对L6骨骼肌细胞摄取葡萄糖能力的影响。已发现代谢产物5-(3,5-二羟基苯基)-γ-戊内酯(EGC-M5)、4-羟基-5-(3,4,5-三羟基苯基)戊酸(EGC-M6)、5-(3,4,5-三羟基苯基)-γ-戊内酯(EGC-M7)和5-(3-羟基苯基)戊酸(EGC-M11)可显著促进L6肌管摄取葡萄糖。EGC-M5是EGCG的主要环裂变代谢产物之一,体内外实验均发现其对骨骼肌中葡萄糖转运蛋白4(GLUT4)转位具有促进作用,同时伴有AMP活化蛋白激酶(AMPK)信号通路的磷酸化。此外,还检测了口服单剂量EGC-M5对ICR小鼠葡萄糖耐量试验的影响,结果观察到高血糖得到显著抑制。这些数据表明EGC-M5在体内具有抗糖尿病作用。

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