Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells
Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells
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DOI：
10.1016/j.fct.2013.11.014
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发表时间：
2014-02-01
影响因子：
4.3
通讯作者：
Ramos, Sonia
中科院分区：
文献类型：
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作者：
Cordero-Herrera, Isabel;Angeles Martin, Maria;Ramos, Sonia
胰岛素抵抗是2型糖尿病的主要特征。可可及其主要的黄烷醇（-）-表儿茶素（EC）显示出一些抗糖尿病作用，但其与肝脏中葡萄糖代谢和胰岛素信号传导相关的预防活动的机制在很大程度上仍然未知。在目前的工作中，EC和可可多酚提取物（CPE）对胰岛素信号转导和葡萄糖的产生和摄取的预防作用进行了研究，在胰岛素敏感的人HepG 2细胞高葡萄糖处理。用EC或CPE预处理细胞恢复了由高糖触发的IR、IRS-1和IRS-2的酪氨酸磷酸化和总水平的降低。EC和CPE预处理还防止了PI 3 K/AKT通路和AMPK的失活，以及由高糖诱导的GLUT-2水平的降低。此外，用EC和CPE预处理细胞避免了由高葡萄糖引起的PEPCK水平的增加和葡萄糖摄取的减少，使葡萄糖产生的增强水平和糖原含量的降低恢复到对照值。这些结果表明，EC和CPE改善了高糖处理的HepG 2的胰岛素敏感性，通过减弱胰岛素信号传导阻滞和调节葡萄糖摄取和产生来预防或延迟潜在的肝功能障碍。(C)2013爱思唯尔有限公司保留所有权利。
Insulin resistance is the primary characteristic of type 2 diabetes. Cocoa and its main flavanol, (-)-epicatechin (EC), display some antidiabetic effects, but the mechanisms for their preventive activities related to glucose metabolism and insulin signalling in the liver remain largely unknown. In the present work, the preventive effect of EC and a cocoa polyphenolic extract (CPE) on insulin signalling and on both glucose production and uptake are studied in insulin-responsive human HepG2 cells treated with high glucose. Pre-treatment of cells with EC or CPE reverted decreased tyrosine-phosphorylated and total levels of IR, IRS-1 and -2 triggered by high glucose. EC and CPE pre-treatment also prevented the inactivation of the PI3K/AKT pathway and AMPK, as well as the diminution of GLUT-2 levels induced by high glucose. Furthermore, pre-treatment of cells with EC and CPE avoided the increase in PEPCK levels and the diminished glucose uptake provoked by high glucose, returning enhanced levels of glucose production and decreased glycogen content to control values. These findings suggest that EC and CPE improved insulin sensitivity of HepG2 treated with high glucose, preventing or delaying a potential hepatic dysfunction through the attenuation of the insulin signalling blockade and the modulation of glucose uptake and production. (C) 2013 Elsevier Ltd. All rights reserved.