Epigallocatechin Gallate

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No. 3 • June 2003

Epigallocatechin Gallate, a Constituent of Green Tea, Mimics Some of the Actions of Insulin

The authors of a recent paper studying antidiabetic agents from plants1 examined the effects of the green tea flavonoid epigallocatechin gallate (EGCG) because it is reported to have glucose-lowering effects in animals, and Zucker rats injected with EGCG have been reported to have decreased obesity and blood glucose levels and increased insulin sensitivity.

The authors state that “A suitable antidiabetic agent should have actions similar to insulin, or it should bypass the defects in insulin action characterized by insulin resistance.” In this study, the researchers found that EGCG has some insulinomimetic effects in hepatoma cells. The insulinlike metabolic effects of EGCG were somewhat delayed and seemed to depend on redox-dependent changes in the cell.

The most exciting finding in the study was that EGCG at a concentration of 25 µM repressed glucose production by the hepatoma cells to basal levels comparably to insulin at the physiological concentration of 10 nM. The researchers found no further glucose-lowering effects by EGCG above 25 µM. One of the big problems in type 2 diabetes and insulin resistance is that certain of the physiological effects of insulin, such as the repression of glucose production and release by hepatic (liver) cells, are impaired. The liver of a diabetic human can convert body protein into glucose at a rate of up to 800 g/day.

The signaling pathways for insulin and EGCG for the repression of glucose production by the hepatoma cells were very similar. As the authors report, insulin activates PI3K, PKB, and p70s6k in H4IIE rat hepatoma cells. Cells were incubated with 50-µM EGCG or with 10-nM insulin for different times, and the effects on these kinases were compared. Effects were similar, but activities were increased by different amounts or at different times. As the researchers note, “The smaller effect of EGCG on the activation of these kinases is equivalent to that observed after treatment of H4IIE cells with 0.0l-nM insulin . . . .”

The researchers report that reactive oxygen species seemed to be increased after treatment of H4IIE cells with EGCG. Apparently, the increase in oxygen radicals is a part of at least some of the effects of EGCG, since treatment of cells with N-acetylcysteine (NAC) or superoxide dismutase (SOD) completely prevented the effect of EGCG on protein-tyrosine phosphorylation, as well as EGCG-mediated PEPCK and G6Pase gene repression. The actions of insulin, however, are mostly unaffected by NAC and SOD.

The authors conclude, “Our results reveal that EGCG is insulinomimetic in that it lowers glucose production in H4IIE cells and decreases the expression of genes that control gluconeogenesis, such as the PEPCK and G6Pase genes. Also, EGCG activates the same kinases as insulin and promotes the phosphorylation of insulin signaling proteins, such as IRS-1 and IR-beta.”

  1. Waltner-Law et al. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem 277(38):34933-40 (2002).

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