酪蛋白衍生三肽 Ile-Pro-Pro 和 Val-Pro-Pro 对肝葡萄糖代谢的分子靶点和机制,Journal of Agricultural and Food Chemistry

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酪蛋白衍生三肽 Ile-Pro-Pro 和 Val-Pro-Pro 对肝葡萄糖代谢的分子靶点和机制
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-11-27 , DOI: 10.1021/acs.jafc.3c06258
Chenyang Wang _{1,

2} , Lin Zheng _{1,

2} , Mouming Zhao _{1,

2,

3}

Affiliation

本研究旨在探讨Ile-Pro-Pro（IPP）和Val-Pro-Pro（VPP）调节肝细胞糖代谢的分子靶点和机制及其在小鼠体内的降血糖活性。结果显示，IPP 和 VPP (600 μM) 均显着增加 HepG2 细胞和原代肝细胞的葡萄糖消耗 ( p < 0.05)。它们还调节葡萄糖代谢酶的活性并增加 HepG2 细胞中p -AKT 和 GLUT2的蛋白表达。IPP直接与胰岛素受体（IR）相互作用，激活胰岛素/AKT信号通路。VPP 对葡萄糖消耗的活性并不归因于 IR 结合，并且通过相似集成和形状相似方法预测了 76 个潜在的抗糖尿病靶点。其中，AKT和MAPK信号通路（其中存在两个枢纽基因AKT1和MAPK4）被评估对VPP对葡萄糖消耗的活性做出了主要贡献。此外，IPP和VPP（300 μmol/kg）均能显着降低小鼠血糖水平（p < 0.05），血糖曲线下面积分别下降约19%±0.09和21%±0.11%。该研究为IPP和VPP作为调节糖代谢紊乱的功能食品的开发提供了新的理论支持。

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Molecular Targets and Mechanisms of Casein-Derived Tripeptides Ile-Pro-Pro and Val-Pro-Pro on Hepatic Glucose Metabolism

The objective of this study was to explore the molecular targets and mechanism of Ile-Pro-Pro (IPP) and Val-Pro-Pro (VPP) on regulating glucose metabolism in hepatic cells and their in vivo hypoglycemic activities in mice. Results showed that both IPP and VPP (600 μM) significantly enhanced the glucose consumption in HepG2 cells and primary hepatocytes (p < 0.05). They also regulated activities of glucose metabolizing enzymes and increased the protein expression of p-AKT and GLUT2 in HepG2 cells. IPP directly interacted with the insulin receptor (IR) to activate the insulin/AKT signaling pathway. The activity of VPP on glucose consumption was not attributed to IR binding, and 76 potential antidiabetic targets were predicted by similarity ensemble and shape similarity approaches. Among them, the AKT and MAPK signaling pathway, in which two hub genes AKT1 and MAPK4 existed, were evaluated to make major contributions to the activity of VPP on glucose consumption. Moreover, both IPP and VPP (300 μmol/kg) could significantly reduce the blood glucose levels in mice (p < 0.05), with blood glucose area under the curve dropping by approximately 19% ± 0.09 and 21% ± 0.11%, respectively. This study provides a new theoretical support for the development of IPP and VPP as functional foods to regulate glucose metabolic disorders.

更新日期：2023-11-27

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