Epicatechin and β-Glucan from Whole Highland Barley Grain Synergistic Benefit on Attenuating Hyperglycemia via Improving Hepatic Glucose Metabolism in Diabetic C57BL/6J Mice,Journal of Agricultural and Food Chemistry

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Epicatechin and β-Glucan from Whole Highland Barley Grain Synergistic Benefit on Attenuating Hyperglycemia via Improving Hepatic Glucose Metabolism in Diabetic C57BL/6J Mice
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-04 , DOI: 10.1021/acs.jafc.4c04791
Zehua Liu _{1,

2} , Zhaowan Zhang ₁ , Ruoxin Tang ₁ , Jianshen Liu ₁ , Yijie Yang ₃

Affiliation

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.

中文翻译：

表儿茶素和全青稞粒中的 β-葡聚糖通过改善糖尿病 C57BL/6J 小鼠的肝葡萄糖代谢对减轻高血糖具有协同作用

我们前期的研究证明，全麦青稞中的表儿茶素（EC）和β-葡聚糖（BG）可以协同调节胰岛素抵抗HepG2细胞的葡萄糖代谢。然而，体内葡萄糖代谢调节的主要目标和机制仍然很大程度上未知。在这项研究中，细胞转染试验和微量热泳分析表明，EC 和 BG 可以分别直接与胰岛素受体 (IR) 和哺乳动物雷帕霉素受体 (mTOR) 结合。分子动力学分析表明结合位点的关键氨基酸为Asp、Met、Val、Lys、Ser和Tys。 EC 补充剂上调 IRS-1/PI3K/Akt 通路，而 BG 上调 mTOR/Akt 通路。值得注意的是，与 EC 和 BG 的单独作用相比，补充 EC + BG 显着增加了 Akt 和葡萄糖转运蛋白 4 型 (GLUT4) 蛋白的表达，同时降低了肝细胞中糖原合成酶激酶 3β (GSK-3β) 的表达，表明它们具有协同作用。具有改善肝脏葡萄糖摄取和糖原合成的作用。一致的是，与 EC 和 BG 相比，补充 EC + BG 显着降低了血糖水平并改善了口服葡萄糖耐量。因此，联合补充EC和BG可能会与相应的受体结合，协同激活Akt表达，从而改善肝脏葡萄糖代谢，从而改善体内高血糖。

更新日期：2024-09-04

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