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Structural characterization and hypoglycemic mechanism of Chinese yam polysaccharide at the nexus of IR-AMPK-PI3K-AKT pathway in type 2 diabetic zebrafish and cellular insulin resistant model.

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Title: Structural characterization and hypoglycemic mechanism of Chinese yam polysaccharide at the nexus of IR-AMPK-PI3K-AKT pathway in type 2 diabetic zebrafish and cellular insulin resistant model.
Authors: Liu X; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China., Ahmed A; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China; Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75272, Pakistan., Zheng H; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Sino-Portugal TCM International Cooperation Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, P. R. China., Wang F; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China., Fan B; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China. Electronic address: fanbei517@163.com., Wang Q; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China; Sino-Portugal TCM International Cooperation Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, P. R. China. Electronic address: wangqiong01@caas.cn.
Source: Food research international (Ottawa, Ont.) [Food Res Int] 2026 Oct 31; Vol. 242 (Pt 5), pp. 120064. Date of Electronic Publication: 2026 Jul 27.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science Country of Publication: Canada NLM ID: 9210143 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7145 (Electronic) Linking ISSN: 09639969 NLM ISO Abbreviation: Food Res Int Subsets: MEDLINE
Imprint Name(s): Original Publication: Ottawa, Ontario, Canada : Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science, c1992-
MeSH Terms: Polysaccharides*/pharmacology , Polysaccharides*/chemistry , Diabetes Mellitus, Type 2*/drug therapy , Diabetes Mellitus, Type 2*/metabolism , Hypoglycemic Agents*/pharmacology , Hypoglycemic Agents*/chemistry , Dioscorea*/chemistry , Insulin Resistance*, Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; Phosphatidylinositol 3-Kinases/metabolism ; AMP-Activated Protein Kinases/metabolism ; Oxidative Stress/drug effects ; Receptor, Insulin/metabolism ; Glucose/metabolism ; Animals ; Zebrafish ; 3T3-L1 Cells ; Mice ; Disease Models, Animal
Abstract: Chinese yam polysaccharides (CYPS) have attracted significant interest for their potential health benefits, particularly in managing diabetes mellitus (T2DM). However, their structural characteristics, antidiabetic mechanisms in insulin-resistant cells, and type 2 diabetic models remain poorly understood. This study aimed to elucidate the structural properties of CYPS using various analytical techniques and to evaluate its antidiabetic mechanism in an insulin-resistant cellular model and a type 2 diabetic zebrafish pre-clinical model. The results demonstrated that CYPS is a neutral pyranose-type polysaccharide containing both α- and β-glycosidic linkages with a random coil conformation. It is a polydisperse mixture comprised of 15 monosaccharides, including D-sorbitol, D-galactose, d-glucose, inositol, and D-mannose. CYPS significantly improved glucose uptake and increased the activity of hexokinase and pyruvate kinase in dexamethasone-induced insulin-resistant 3 T3-L1 adipocytes. Moreover, CYPS treatment markedly reduced whole-larvae glucose levels, ameliorated dyslipidemia, and improved the activities of hexokinase and pyruvate kinase to support glucose metabolism. CYPS also reduced oxidative stress by increasing glutathione peroxidase activity and decreasing malondialdehyde levels. Mechanistically, CYPS enhanced the expression of PI3K, Akt, AMPK, and IRS1 in diabetic zebrafish and dexamethasone-treated insulin-resistant cells - key factors for insulin sensitivity, glucose metabolism, energy balance, and downstream cellular functions. Thereby, it influences important genes and proteins within the AMPK-PI3K/Akt signaling pathway. These findings strongly suggest that polydisperse CYPS significantly improves insulin sensitivity and glucose homeostasis in type 2 diabetic zebrafish by targeting AMPK-PI3K/Akt pathway and could be a promising candidate to be explored further as a functional therapeutic food for T2DM management.
(Copyright © 2026. Published by Elsevier Ltd.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Chinese yam polysaccharides; Diabetic zebrafish model; Insulin resistance
Substance Nomenclature: 0 (Polysaccharides)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (Hypoglycemic Agents)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
EC 2.7.10.1 (Receptor, Insulin)
IY9XDZ35W2 (Glucose)
Entry Date(s): Date Created: 20260824 Date Completed: 20260824 Latest Revision: 20260824
Update Code: 20260825
DOI: 10.1016/j.foodres.2026.120064
PMID: 42637318
Database: MEDLINE
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  Data: Structural characterization and hypoglycemic mechanism of Chinese yam polysaccharide at the nexus of IR-AMPK-PI3K-AKT pathway in type 2 diabetic zebrafish and cellular insulin resistant model.
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  Data: <searchLink fieldCode="AU" term="%22Liu+X%22">Liu X</searchLink>; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China.<br /><searchLink fieldCode="AU" term="%22Ahmed+A%22">Ahmed A</searchLink>; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China; Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75272, Pakistan.<br /><searchLink fieldCode="AU" term="%22Zheng+H%22">Zheng H</searchLink>; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Sino-Portugal TCM International Cooperation Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, P. R. China.<br /><searchLink fieldCode="AU" term="%22Wang+F%22">Wang F</searchLink>; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China.<br /><searchLink fieldCode="AU" term="%22Fan+B%22">Fan B</searchLink>; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China. Electronic address: fanbei517@163.com.<br /><searchLink fieldCode="AU" term="%22Wang+Q%22">Wang Q</searchLink>; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, P. R. China; Sino-Portugal TCM International Cooperation Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, P. R. China. Electronic address: wangqiong01@caas.cn.
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  Data: <searchLink fieldCode="JN" term="%229210143%22">Food research international (Ottawa, Ont.)</searchLink> [Food Res Int] 2026 Oct 31; Vol. 242 (Pt 5), pp. 120064. <i>Date of Electronic Publication: </i>2026 Jul 27.
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  Data: <i>Original Publication</i>: Ottawa, Ontario, Canada : Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science, c1992-
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  Data: <searchLink fieldCode="MM" term="%22Polysaccharides%22">Polysaccharides*</searchLink>/<searchLink fieldCode="MM" term="%22Polysaccharides+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Polysaccharides%22">Polysaccharides*</searchLink>/<searchLink fieldCode="MM" term="%22Polysaccharides+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Type+2%22">Diabetes Mellitus, Type 2*</searchLink>/<searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Type+2+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Type+2%22">Diabetes Mellitus, Type 2*</searchLink>/<searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Type+2+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Hypoglycemic+Agents%22">Hypoglycemic Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Hypoglycemic+Agents+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Hypoglycemic+Agents%22">Hypoglycemic Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Hypoglycemic+Agents+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Dioscorea%22">Dioscorea*</searchLink>/<searchLink fieldCode="MM" term="%22Dioscorea+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Insulin+Resistance%22">Insulin Resistance*</searchLink><br /><searchLink fieldCode="MH" term="%22Proto-Oncogene+Proteins+c-akt%22">Proto-Oncogene Proteins c-akt</searchLink>/<searchLink fieldCode="MH" term="%22Proto-Oncogene+Proteins+c-akt+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Signal+Transduction%22">Signal Transduction</searchLink>/<searchLink fieldCode="MH" term="%22Signal+Transduction+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Phosphatidylinositol+3-Kinases%22">Phosphatidylinositol 3-Kinases</searchLink>/<searchLink fieldCode="MH" term="%22Phosphatidylinositol+3-Kinases+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22AMP-Activated+Protein+Kinases%22">AMP-Activated Protein Kinases</searchLink>/<searchLink fieldCode="MH" term="%22AMP-Activated+Protein+Kinases+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Oxidative+Stress%22">Oxidative Stress</searchLink>/<searchLink fieldCode="MH" term="%22Oxidative+Stress+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Receptor%2C+Insulin%22">Receptor, Insulin</searchLink>/<searchLink fieldCode="MH" term="%22Receptor%2C+Insulin+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Glucose%22">Glucose</searchLink>/<searchLink fieldCode="MH" term="%22Glucose+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Zebrafish%22">Zebrafish</searchLink> ; <searchLink fieldCode="MH" term="%223T3-L1+Cells%22">3T3-L1 Cells</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Disease+Models%2C+Animal%22">Disease Models, Animal</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Chinese yam polysaccharides (CYPS) have attracted significant interest for their potential health benefits, particularly in managing diabetes mellitus (T2DM). However, their structural characteristics, antidiabetic mechanisms in insulin-resistant cells, and type 2 diabetic models remain poorly understood. This study aimed to elucidate the structural properties of CYPS using various analytical techniques and to evaluate its antidiabetic mechanism in an insulin-resistant cellular model and a type 2 diabetic zebrafish pre-clinical model. The results demonstrated that CYPS is a neutral pyranose-type polysaccharide containing both α- and β-glycosidic linkages with a random coil conformation. It is a polydisperse mixture comprised of 15 monosaccharides, including D-sorbitol, D-galactose, d-glucose, inositol, and D-mannose. CYPS significantly improved glucose uptake and increased the activity of hexokinase and pyruvate kinase in dexamethasone-induced insulin-resistant 3 T3-L1 adipocytes. Moreover, CYPS treatment markedly reduced whole-larvae glucose levels, ameliorated dyslipidemia, and improved the activities of hexokinase and pyruvate kinase to support glucose metabolism. CYPS also reduced oxidative stress by increasing glutathione peroxidase activity and decreasing malondialdehyde levels. Mechanistically, CYPS enhanced the expression of PI3K, Akt, AMPK, and IRS1 in diabetic zebrafish and dexamethasone-treated insulin-resistant cells - key factors for insulin sensitivity, glucose metabolism, energy balance, and downstream cellular functions. Thereby, it influences important genes and proteins within the AMPK-PI3K/Akt signaling pathway. These findings strongly suggest that polydisperse CYPS significantly improves insulin sensitivity and glucose homeostasis in type 2 diabetic zebrafish by targeting AMPK-PI3K/Akt pathway and could be a promising candidate to be explored further as a functional therapeutic food for T2DM management.<br /> (Copyright © 2026. Published by Elsevier Ltd.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Chinese yam polysaccharides; Diabetic zebrafish model; Insulin resistance
– Name: NumberCAS
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  Data: 0 (Polysaccharides)<br />EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)<br />0 (Hypoglycemic Agents)<br />EC 2.7.1.- (Phosphatidylinositol 3-Kinases)<br />EC 2.7.11.31 (AMP-Activated Protein Kinases)<br />EC 2.7.10.1 (Receptor, Insulin)<br />IY9XDZ35W2 (Glucose)
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  Data: 10.1016/j.foodres.2026.120064
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        Value: 10.1016/j.foodres.2026.120064
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 120064
    Subjects:
      – SubjectFull: Proto-Oncogene Proteins c-akt metabolism
        Type: general
      – SubjectFull: Signal Transduction drug effects
        Type: general
      – SubjectFull: Phosphatidylinositol 3-Kinases metabolism
        Type: general
      – SubjectFull: AMP-Activated Protein Kinases metabolism
        Type: general
      – SubjectFull: Oxidative Stress drug effects
        Type: general
      – SubjectFull: Receptor, Insulin metabolism
        Type: general
      – SubjectFull: Glucose metabolism
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Zebrafish
        Type: general
      – SubjectFull: 3T3-L1 Cells
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Disease Models, Animal
        Type: general
      – SubjectFull: Polysaccharides pharmacology
        Type: general
      – SubjectFull: Polysaccharides chemistry
        Type: general
      – SubjectFull: Diabetes Mellitus, Type 2 drug therapy
        Type: general
      – SubjectFull: Diabetes Mellitus, Type 2 metabolism
        Type: general
      – SubjectFull: Hypoglycemic Agents pharmacology
        Type: general
      – SubjectFull: Hypoglycemic Agents chemistry
        Type: general
      – SubjectFull: Dioscorea chemistry
        Type: general
      – SubjectFull: Insulin Resistance
        Type: general
    Titles:
      – TitleFull: Structural characterization and hypoglycemic mechanism of Chinese yam polysaccharide at the nexus of IR-AMPK-PI3K-AKT pathway in type 2 diabetic zebrafish and cellular insulin resistant model.
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              Text: 2026 Oct 31
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