Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production.
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.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Mary E
ME
Waltner-Law
Xiaohui L
XL
Wang
Brian K
BK
Law
Robert K
RK
Hall
Masao
M
Nawano
Daryl K
DK
Granner
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000096:biosynthesis*; D005952:Glucose-6-Phosphatase / Q000235:genetics; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D014443:Tyrosine; D002392:Catechin; C045651:epigallocatechin gallate; D013482:Superoxide Dismutase; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases; D005952:Glucose-6-Phosphatase; D005947:Glucose; D000111:Acetylcysteine