The Hypoglycemic Activity of <i>Gracilaria lemaneiformis</i> Polysaccharide Gels Based on IR/IRS-2/PI3k/Akt/Glut4 and Glycometabolism Signaling Pathways in HepG2 Cells

The Hypoglycemic Activity of <i>Gracilaria lemaneiformis</i> Polysaccharide Gels Based on IR/IRS-2/PI3k/Akt/Glut4 and Glycometabolism Signaling Pathways in HepG2 Cells

The aim of this study was to investigate the hypoglycemic activity and mechanism of <i>G. lemaneiformis</i> polysaccharide gels (GLP and GLP-HV) based on IR/IRS-2/PI3k/Akt/Glut4 and glycometabolism signaling pathways in HepG2 cells. After H<sub>2</sub>O<sub>2</sub>...

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Bibliographic Details
Main Authors: Xiaoshan Long, Shucheng Liu, Xianqing Yang, Yongqiang Zhao, Shaoling Yang, Ya Wei, Chuang Pan, Shengjun Chen, Peihong Jiang, Bo Qi, Xiao Hu
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Gels
Subjects:
polysaccharides gels
hypoglycemic mechanism
molecular weight
correlation analysis
Online Access:https://www.mdpi.com/2310-2861/11/5/366
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Summary:The aim of this study was to investigate the hypoglycemic activity and mechanism of <i>G. lemaneiformis</i> polysaccharide gels (GLP and GLP-HV) based on IR/IRS-2/PI3k/Akt/Glut4 and glycometabolism signaling pathways in HepG2 cells. After H<sub>2</sub>O<sub>2</sub>-Vc degradation, the molecular weight of <i>G. lemaneiformis</i> 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. <i>G. lemaneiformis</i> 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 <i>G. lemaneiformis</i> 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 <i>G. lemaneiformis</i> 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 <i>G. lemaneiformis</i> 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.
ISSN:2310-2861

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