基于IR/IRS-2/PI3k/Akt/Glut4和糖代谢信号通路的多糖凝胶在HepG2细胞中的降血糖活性

The Hypoglycemic Activity of Polysaccharide Gels Based on IR/IRS-2/PI3k/Akt/Glut4 and Glycometabolism Signaling Pathways in HepG2 Cells.

作者信息

Long Xiaoshan, Liu Shucheng, Yang Xianqing, Zhao Yongqiang, Yang Shaoling, Wei Ya, Pan Chuang, Chen Shengjun, Jiang Peihong, Qi Bo, Hu Xiao

机构信息

Key Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, China.

Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.

出版信息

Gels. 2025 May 15;11(5):366. doi: 10.3390/gels11050366.

DOI:10.3390/gels11050366

PMID:40422385

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12110834/

Abstract

The aim of this study was to investigate the hypoglycemic activity and mechanism of polysaccharide gels (GLP and GLP-HV) based on IR/IRS-2/PI3k/Akt/Glut4 and glycometabolism signaling pathways in HepG2 cells. After HO-Vc degradation, the molecular weight of polysaccharide gel declined from 1478 kDa to 16 kDa. Molecular weight chromatogram and distribution indicated that GLP-HV had a high molecular weight homogeneity compared to GLP. polysaccharide gels significantly decreased the TC, TG, LDL-C, MDA, and LDH contents and enhanced the activities of HDL-C, T-AOC, CAT, GSH-PX, SOD, insulin, and glycogen in HepG2 cells. Fluorescent staining results showed that polysaccharide gels reduced ROS and calcium ions levels in HepG2 cells. GLP and GLP-HV displayed excellent hypoglycemic activity, with GLP-HV performing better. Furthermore, qPCR and Western blot analysis revealed that polysaccharide gels remarkably strengthened the levels of IR, IRS-2, PI3K, Akt, Glut4, HK, G6PD, PFK, PEPCK, GK, PK genes, and proteins. Spearman's correlation analysis revealed that the IR/IRS-2/PI3k/Akt/Glut4 signaling pathway played a dominant role in regulating activity. These results show that polysaccharide gels present a prominent hypoglycemic effect mediated by the IR/IRS-2/PI3k/Akt/Glut4 and glycometabolism signaling pathways, with the former playing a dominant role.

摘要

本研究旨在基于IR/IRS-2/PI3k/Akt/Glut4和糖代谢信号通路，研究多糖凝胶（GLP和GLP-HV）在HepG2细胞中的降血糖活性及机制。经HO-Vc降解后，多糖凝胶的分子量从1478 kDa降至16 kDa。分子量色谱图和分布表明，与GLP相比，GLP-HV具有较高的分子量同质性。多糖凝胶显著降低了HepG2细胞中TC、TG、LDL-C、MDA和LDH的含量，并增强了HDL-C、T-AOC、CAT、GSH-PX、SOD、胰岛素和糖原的活性。荧光染色结果表明，多糖凝胶降低了HepG2细胞中的ROS和钙离子水平。GLP和GLP-HV表现出优异的降血糖活性，其中GLP-HV效果更佳。此外，qPCR和蛋白质免疫印迹分析显示，多糖凝胶显著提高了IR、IRS-2、PI3K、Akt、Glut4、HK、G6PD、PFK、PEPCK、GK、PK基因和蛋白质的水平。Spearman相关性分析表明，IR/IRS-2/PI3k/Akt/Glut4信号通路在调节活性中起主导作用。这些结果表明，多糖凝胶通过IR/IRS-2/PI3k/Akt/Glut4和糖代谢信号通路呈现出显著的降血糖作用，其中前者起主导作用。