糖原合酶
蛋白激酶B
葡萄糖转运蛋白
过剩4
新陈代谢
PI3K/AKT/mTOR通路
碳水化合物代谢
糖原
胰岛素受体
下调和上调
葛兰素史克-3
胰岛素
化学
内分泌学
内科学
生物化学
生物
胰岛素抵抗
医学
信号转导
基因
作者
Zehua Liu,Zhaowan Zhang,Ruoxin Tang,Jianshen Liu,Yijie Yang
标识
DOI:10.1021/acs.jafc.4c04791
摘要
Our previous study proved that epicatechin (EC) and β-glucan (BG) from whole-grain highland barley synergistically modulate glucose metabolism in insulin-resistant HepG2 cells. However, the main target and the mechanism underlying the modulation of glucose metabolism in vivo remain largely unknown. In this study, cell transfection assay and microscale thermophoresis analysis revealed that EC and BG could directly bind to the insulin receptor (IR) and mammalian receptor for rapamycin (mTOR), respectively. Molecular dynamic analysis indicated that the key amino acids of binding sites were Asp, Met, Val, Lys, Ser, and Tys. EC supplementation upregulated the IRS-1/PI3K/Akt pathway, while BG upregulated the mTOR/Akt pathway. Notably, supplementation with EC + BG significantly increased Akt and glucose transporter type 4 (GLUT4) protein expressions, while decreasing glycogen synthase kinase 3β (GSK-3β) expression in liver cells as compared to the individual effects of EC and BG, indicating their synergistic effect on improving hepatic glucose uptake and glycogen synthesis. Consistently, supplementation with EC + BG significantly decreased blood glucose levels and improved oral glucose tolerance compared to EC and BG. Therefore, combined supplementation with EC and BG may bind to corresponding receptors, targeting synergistic activation of Akt expression, leading to the improvement of hepatic glucose metabolism and thereby ameliorating hyperglycemia in vivo.
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