Epigallocatechin gallate (EGCG) mimics insulin action on the transcription factor FOXO1 a and elicits cellular responses in the presence and absence of insulin
Epigallocatechin gallate (EGCG) mimics insulin action on the transcription factor FOXO1 a and elicits cellular responses in the presence and absence of insulin
复制标题
DOI：
10.1016/j.cellsig.2006.07.008
复制
发表时间：
2007-02-01
影响因子：
4.8
通讯作者：
Rena, Graham
中科院分区：
文献类型：
--
作者：
Anton, Siobhan;Melville, Laura;Rena, Graham
绿色茶类黄酮表没食子儿茶素没食子酸酯（EGCG）是已报道在哺乳动物中具有胰岛素样降糖特性的几种化合物之一。据了解，EGCG至少部分地通过抑制致炎基因如磷酸烯醇丙酮酸羧激酶起作用，但靶向实现这一点的转录因子尚不清楚。我们在这里表明，表没食子儿茶素没食子酸酯诱导的胰岛素敏感残基的转录因子FOXO 1a的磷酸化。与胰岛素类似，EGCG诱导的FOXO 1a磷酸化被PtdIns 3-激酶抑制剂LY 294002消除，但不被PD 98059（促分裂原活化蛋白激酶级联抑制剂）或雷帕霉素（p70 S6激酶信号传导抑制剂）消除。然而，EGCG不同于胰岛素和IGF-1，因为其对FOXO 1a磷酸化的诱导对活性氧（ROS）的清除剂敏感。这些结果表明，EGCG通过与胰岛素和IGF-1诱导的FOXO磷酸化类似但不相同的机制，至少部分地通过FOXO磷酸化发挥其胰岛素模拟作用。我们的研究结果表明，以EGCG的方式发挥作用的药物可能是有用的抗糖尿病药物。(c)2006年爱思唯尔公司All rights reserved.
The green tea flavonoid epigallocatechin gallate (EGCG) is one of several compounds that have been reported to have insulin-like glucose-lowering properties in mammals. EGCG is understood to act at least in part by repression of gluconeogenic genes such as phosphoenolpyruvate carboxykinase but the transcription factors that are targeted to achieve this are unknown. We show here that EGCG induces phosphorylation of insulin-sensitive residues on the transcription factor FOXO1a. Like insulin, EGCG induced FOXO1a phosphorylation is abolished by the PtdIns 3-kinase inhibitor LY294002 but not by PD98059 (an inhibitor of mitogen-activated protein kinase cascade) or by rapamycin (an inhibitor of signalling to p70 S6 kinase). EGCG differs from insulin and IGF-1 however, in that its induction of FOXO1a phosphorylation is sensitive to scavengers of reactive oxygen species (ROS). These results indicate that EGCG exerts its insulin mimetic effects at least in part by phosphorylation of the FOXOs through a mechanism that is similar but not identical to insulin and IGF-1 induced FOXO phosphorylation. Our results suggest that agents acting in the manner of EGCG may be useful antidiabetic agents. (c) 2006 Elsevier Inc. All rights reserved.