Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells
Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells
复制标题
DOI：
10.1002/mnfr.201200500
复制
发表时间：
2013-06-01
影响因子：
5.2
通讯作者：
Ramos, Sonia
中科院分区：
文献类型：
--
作者：
Cordero-Herrera, Isabel;Angeles Martin, Maria;Ramos, Sonia
范围可可和（-）-表儿茶素（EC），一种主要的可可黄烷醇，已被认为在糖尿病中发挥有益作用，但其胰岛素样作用的机制仍然未知。在这项研究中，通过分析胰岛素途径的关键蛋白，即胰岛素受体，胰岛素受体底物（IRS）1和2，PI 3 K/AKT和5-AMP-活化的蛋白激酶（AMPK），以及葡萄糖转运蛋白GLUT-2和肝脏葡萄糖产生的水平，研究了EC和可可酚提取物（CPE）对肝HepG 2细胞胰岛素信号转导的调节。方法和结果EC和CPE可增强HepG 2细胞的酪氨酸磷酸化水平和总胰岛素受体、IRS-1和IRS-2水平，激活PI 3 K/AKT通路和AMPK。CPE还提高了GLUT-2的水平。有趣的是，EC和CPE调节磷酸烯醇式丙酮酸羧激酶的表达，这是一种参与胚胎发育的关键蛋白，导致葡萄糖产生减少。此外，阻断AKT和AMPK可阻止EC和CPE调节的肝脏新生。结论EC和CPE通过激活胰岛素信号通路的关键蛋白，并通过调节AKT和AMPK来调节HepG 2细胞葡萄糖的分泌，从而增强胰岛素信号通路。
Scope Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in diabetes, but the mechanism for their insulin-like effects remains unknown. In this study, the modulation of insulin signalling by EC and a cocoa phenolic extract (CPE) on hepatic HepG2 cells was investigated by analysing key proteins of the insulin pathways, namely insulin receptor, insulin receptor substrate (IRS) 1 and 2, PI3K/AKT and 5-AMP-activated protein kinase (AMPK), as well as the levels of the glucose transporter GLUT-2 and the hepatic glucose production. Methods and results EC and CPE enhanced the tyrosine phosphorylation and total insulin receptor, IRS-1 and IRS-2 levels and activated the PI3K/AKT pathway and AMPK in HepG2 cells. CPE also enhanced the levels of GLUT-2. Interestingly, EC and CPE modulated the expression of phosphoenolpyruvate carboxykinase, a key protein involved in the gluconeogenesis, leading to a diminished glucose production. In addition, EC- and CPE-regulated hepatic gluconeogenesis was prevented by the blockage of AKT and AMPK. Conclusion Our data suggest that EC and CPE strengthen the insulin signalling by activating key proteins of that pathway and regulating glucose production through AKT and AMPK modulation in HepG2 cells.