Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production

J Biol Chem. 2002 Sep 20;277(38):34933-40. doi: 10.1074/jbc.M204672200. Epub 2002 Jul 12.

Abstract

Herbs have been used for medicinal purposes, including the treatment of diabetes, for centuries. Plants containing flavonoids are used to treat diabetes in Indian medicine and the green tea flavonoid, epigallocatechin gallate (EGCG), is reported to have glucose-lowering effects in animals. We show here that the regulation of hepatic glucose production is decreased by EGCG. Furthermore, like insulin, EGCG increases tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), and it reduces phosphoenolpyruvate carboxykinase gene expression in a phosphoinositide 3-kinase-dependent manner. EGCG also mimics insulin by increasing phosphoinositide 3-kinase, mitogen-activated protein kinase, and p70(s6k) activity. EGCG differs from insulin, however, in that it affects several insulin-activated kinases with slower kinetics. Furthermore, EGCG regulates genes that encode gluconeogenic enzymes and protein-tyrosine phosphorylation by modulating the redox state of the cell. These results demonstrate that changes in the redox state may have beneficial effects for the treatment of diabetes and suggest a potential role for EGCG, or derivatives, as an antidiabetic agent.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Catechin / analogs & derivatives
  • Catechin / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gluconeogenesis / drug effects*
  • Glucose / biosynthesis*
  • Glucose-6-Phosphatase / genetics
  • Insulin / pharmacology
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Liver Neoplasms, Experimental / enzymology
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Rats
  • Signal Transduction / drug effects
  • Superoxide Dismutase / pharmacology
  • Tumor Cells, Cultured
  • Tyrosine / metabolism

Substances

  • Insulin
  • Tyrosine
  • Catechin
  • epigallocatechin gallate
  • Superoxide Dismutase
  • phosphoenolpyruvate carboxylase kinase
  • Protein-Serine-Threonine Kinases
  • Glucose-6-Phosphatase
  • Glucose
  • Acetylcysteine