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J. Biol. Chem., Vol. 277, Issue 38, 34933-34940, September 20, 2002
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From the 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 p70s6k
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.
Epigallocatechin Gallate, a Constituent of Green Tea, Represses
Hepatic Glucose Production*
,,,, and¶
Department of Molecular Physiology and
Biophysics, § Vanderbilt-Ingram Cancer Center, Vanderbilt
University School of Medicine, and the ¶ Veterans Affairs
Hospital, Nashville, Tennessee 37232-0615
*
This work was supported by National Institutes of Health
Grants DK02887 (to M. W.-L.), DK35107 (to D. K. G.) and the Veterans Affairs Research Service.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Molecular
Physiology and Biophysics, 707 Light Hall, Vanderbilt University School
of Medicine, Nashville, TN 37232-0615. Tel.: 615-322-7004; Fax:
615-322-7236; E-mail: daryl.granner@mcmail.vanderbilt.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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