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

Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production
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DOI:
10.1074/jbc.m204672200
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发表时间:
2002-09-20
影响因子:
4.8
通讯作者:
Granner, DK
Granner, DK
中科院分区:
生物学2区
文献类型:
--
作者:
Waltner-Law, ME;Wang, XHL;Granner, DK

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几个世纪以来,草药一直用于医学目的,包括治疗糖尿病。在印度医学中,含有类黄酮的植物被用于治疗糖尿病,据报道,绿色茶类黄酮表没食子儿茶素没食子酸酯(EGCG)在动物中具有降糖作用。我们在这里表明,调节肝脏葡萄糖的生产是由表没食子儿茶素降低。此外,像胰岛素一样,EGCG增加胰岛素受体和胰岛素受体底物-1(IRS-1)的酪氨酸磷酸化,并以磷酸肌醇3-激酶依赖性方式降低磷酸烯醇丙酮酸羧激酶基因表达。EGCG还通过增加磷酸肌醇3-激酶、促分裂原活化蛋白激酶和p70(s6 k)活性来模拟胰岛素。然而,EGCG不同于胰岛素,因为它以较慢的动力学影响几种胰岛素激活的激酶。此外,表没食子儿茶素没食子酸酯通过调节细胞的氧化还原状态来调节编码促凋亡酶和蛋白质酪氨酸磷酸化的基因。这些结果表明,氧化还原状态的变化可能对糖尿病的治疗具有有益的作用,并表明EGCG或其衍生物作为抗糖尿病药物的潜在作用。
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.