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

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.

Keywords: glucose tolerance; glucose transporter 4; metabolite; tea catechin; γ-valerolactone.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / metabolism
  • Catechin / pharmacology
  • Cell Line
  • Gastrointestinal Microbiome
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Hypoglycemic Agents
  • Lactones / metabolism
  • Lactones / pharmacology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism*
  • Myoblasts, Skeletal / drug effects*
  • Myoblasts, Skeletal / metabolism*
  • Phosphorylation
  • Signal Transduction / drug effects

Substances

  • 5-(3,5-dihydroxyphenyl)-gamma-valerolactone
  • Blood Glucose
  • Hypoglycemic Agents
  • Lactones
  • Catechin
  • epigallocatechin gallate
  • AMP-Activated Protein Kinases
  • Glucose
  • gamma-valerolactone