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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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
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Online Access:https://www.mdpi.com/2310-2861/11/5/366
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author Xiaoshan Long
Shucheng Liu
Xianqing Yang
Yongqiang Zhao
Shaoling Yang
Ya Wei
Chuang Pan
Shengjun Chen
Peihong Jiang
Bo Qi
Xiao Hu
author_facet Xiaoshan Long
Shucheng Liu
Xianqing Yang
Yongqiang Zhao
Shaoling Yang
Ya Wei
Chuang Pan
Shengjun Chen
Peihong Jiang
Bo Qi
Xiao Hu
author_sort Xiaoshan Long
collection DOAJ
description 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.
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spelling doaj-art-bedbbd1f549046e09290d697598a9ad92025-08-20T03:14:36ZengMDPI AGGels2310-28612025-05-0111536610.3390/gels11050366The Hypoglycemic Activity of <i>Gracilaria lemaneiformis</i> Polysaccharide Gels Based on IR/IRS-2/PI3k/Akt/Glut4 and Glycometabolism Signaling Pathways in HepG2 CellsXiaoshan Long0Shucheng Liu1Xianqing Yang2Yongqiang Zhao3Shaoling Yang4Ya Wei5Chuang Pan6Shengjun Chen7Peihong Jiang8Bo Qi9Xiao Hu10Key Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaGuangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaShandong Key Laboratory of Storage and Transportation Technology of Agricultural Products, Shandong Institute of Commerce and Technology, Jinan 250103, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaKey Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, ChinaThe 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.https://www.mdpi.com/2310-2861/11/5/366polysaccharides gelshypoglycemic mechanismmolecular weightcorrelation analysis
spellingShingle Xiaoshan Long
Shucheng Liu
Xianqing Yang
Yongqiang Zhao
Shaoling Yang
Ya Wei
Chuang Pan
Shengjun Chen
Peihong Jiang
Bo Qi
Xiao Hu
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
Gels
polysaccharides gels
hypoglycemic mechanism
molecular weight
correlation analysis
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort hypoglycemic activity of i gracilaria lemaneiformis i polysaccharide gels based on ir irs 2 pi3k akt glut4 and glycometabolism signaling pathways in hepg2 cells
topic polysaccharides gels
hypoglycemic mechanism
molecular weight
correlation analysis
url https://www.mdpi.com/2310-2861/11/5/366
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