Skip to main content
SpringerLink
Log in

A polysaccharide from Grifola frondosa relieves insulin resistance of HepG2 cell by Akt-GSK-3 pathway

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Grifola frondosa is an important fungal research resource. However, there was little report about hyperglycemic activity of Grifola frondosa polysaccharide on insulin resistance in vitro. In this study, the hypoglycemic activity of a polysaccharide obtained from Grifola frondosa (GFP) on HepG2 cell and hpyerglycemic mechanism were investigated. The purity of the isolated polysaccharides was examined by HPLC. In this research, it was found that GFP enhanced the absorption of glucose of HepG2 cells in a dose dependent manner at 24 h of 30 ugmL−1. GC-MS and FT-IR spectroscopy analysis results showed that glucose and galactose were the dominant monosaccharides in GFP and the major component of GFP was β-pyranoside. Western-blotting results showed that the HepG2 cell model treated with GFP activated the insulin receptor protein (IRS) in the cell membrane and increased phosphorylated-AktSer473 expression, which had an inhibition of glycogen synthase kinase (GSK-3). The down-regulation of GSK-3 stimulated synthesis of intracellular glycogen. The results above suggested that the GFP increased the metabolism of glucose and stimulated synthesis of intracellular glycogen through the Akt/GSK-3 pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Bae, I.Y., Kim, H.Y., Lee, S., Lee, H.G.: Effect of the degree of oxidation on the physicochemical and biological properties of Grifola frondosa polysaccharides. Carbohydr. Polym. 83, 1298–1302 (2011)

    Article  CAS  Google Scholar 

  2. Cao, X.H., Wang, A.H., Jiao, R.Z., Wang, C.L., Mao, D.Z., Yan, L., et al.: Surfactin induces apoptosis and G2/M arrest in human breast cancer MCF-7 cells through cell cycle factor regulation. Cell Biochem. Biophys. 55(3), 163–171 (2009)

    Article  CAS  PubMed  Google Scholar 

  3. Chen, Q., Xia, Y.P., Qu, Z.Y.: Effects of ecdysteron on insulin sensitivity and Glc metabolism in insulin resistant cell model. Chin. Pharmacol. Bull. 22(4), 465–470 (2006)

    Google Scholar 

  4. Cross, D.A., Alessi, D.R., Cohen, P., Andjelkovich, M., Hemmings, B.A.: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378, 785–789 (1995)

    Article  CAS  PubMed  Google Scholar 

  5. Cui, F.J., Tao, W.Y., Xu, Z.H., Guo, W.J., Xu, H.Y., Ao, Z.H., et al.: Structural analysis of anti-tumor heteropolysaccharide GFPS1b from the cultured mycelia of Grifola frondosa GF9801. Bioresour. Technol. 98, 395–401 (2007)

    Article  CAS  PubMed  Google Scholar 

  6. Defronzo, R.A., Bondonna, R.C., Ferranini, E.: Pathogenesis of NIDDM: a balanced overview. Diabetes Care 15, 318–337 (1992)

    Article  CAS  PubMed  Google Scholar 

  7. Eldar-Finkelman, H., Krebs, E.G.: Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action. Proc. Natl. Acad. Sci. U. S. A. 94, 960–9664 (1997)

    Article  Google Scholar 

  8. Elstrom, R.L., Bauer, D.E., Buzzai, M., Karnauskas, R., Harris, M.H., Plas, D.R., Zhuang, H., Cinalli, R.M., Alavi, A., Rudin, C.M., Thompson, C.B.: Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64, 3892–3899 (2004)

    Article  CAS  PubMed  Google Scholar 

  9. Fellah, A., Anjukandi, P., Waterland, M.R., Williams, M.A.K.: Determining the degree of methylesterification of pectin by ATR/FT-IR: Methodology optimization and comparison with theoretical calculations. Carbohydr. Polym. 78, 847–853 (2009)

    Article  CAS  Google Scholar 

  10. Li, F., Yuan, Q., Rashid, F.: Isolation, purification and immunobiological activity of an new water-soluble bee pollen polysaccharide from Crataegus pinnatifida Bge. Carbohydr. Polym. 78, 80–88 (2009)

  11. Ge, Y., Duan, Y.F., Fang, G.Z., Zhang, Y., Wang, S.: Polysaccharides from fruit calyx of Physalis alkekengi var. francheti: Isolation, purification, structural features and antioxidant activities. Carbohydr. Polym. 77, 188–193 (2009)

    Article  CAS  Google Scholar 

  12. Gu, C.Q., Li, J., Chao, F.H.: Inhibition of hepatitis B virus by D-fraction from Grifola frondosa: Synergistic effect of combination with interferon-alpha in HepG2.2.15. Antivir. Res. 72(2), 162–165 (2006)

    Article  CAS  PubMed  Google Scholar 

  13. Guo, L.M., Zhang, R.X., Jia, Z.P., et al.: Effects of rehmannia glutinosa oligosaccharides on pro liferation of HepG2 and insulin resistant. Chin. J. Chin. Mater. Med. 32(13), 1328–1332 (2007)

    Google Scholar 

  14. Hnatyszyn, O., Mino, J., Ferraro, G., Acevedo, C.: The hypoglycemic effect of Phyllanthus sellowianus fractions in streptozotocin- induced diabetic mice. Phytomedicine 9, 556–559 (2002)

    Article  CAS  PubMed  Google Scholar 

  15. Kurushima, H., Kodama, N., Nanba, H.: Activities of polysaccharides obtain form Grifola frondosa on insulin-dependent diabetes mellitus induced by streptozotocin in mice. Mycoscience 41, 437–480 (2000)

    Article  Google Scholar 

  16. Kubo, K.: Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake). Chem. Pharm. Bull. 17, 1106 (1990)

    Article  Google Scholar 

  17. LeRoith, D., Gavrilova, O.: Mouse models created to study the pathophysiology of type 2 diabetes. Int. J. Biochem. Cell Biol. 38, 904–912 (2006)

    Article  CAS  PubMed  Google Scholar 

  18. Wang, L.-Y., Wang, Y., De-Sheng, X., Ruan, K.-F., Feng, Y., Wang, S.: MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model. J. Ethnopharmacol. 143, 347–354 (2012)

    Article  CAS  PubMed  Google Scholar 

  19. Liu, X.H., Dong, Z., Fu, J.M., et al.: Effects of batephrine on insulin resisitance in HepG2 cells and its mechanism. Chin. J. New. Drugs. 17(12), 1026–1029 (2008)

    CAS  Google Scholar 

  20. Manning, B.D., Cantley, L.C.: AKT/PKB signaling: navigating downstream. Cell 129, 1261–1274 (2007)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Mu, Y.M., Jin, M.M., Chi, C., Lu, J.M., Pan, C.Y.: Therapeutic effects of rhein on the insulin resistance in liver of diabetic rats induced by streptozotocin. Diabetes 57, 717 (2008)

    Google Scholar 

  22. Xie, J.T., Zhou, Y.P.: Ginseng beery reduces blood glucose and body weight in db/db mice. Phytomedicine 9, 254–258 (2002)

    Article  CAS  PubMed  Google Scholar 

  23. Xu, J.S., Ma, M.W., Purcell, W.M.: Characterisation of some cytotoxic endpoints using rat liver and HepG2 spheroids as in vitro models and their application in hepatotoxicity studies. I. Glucose metabolism and enzyme release as cytotoxic markers. Toxicol. Appl. Pharmacol. 189, 100–111 (2003)

    Article  CAS  PubMed  Google Scholar 

  24. Xu, D.S., Feng, Y., Lin, X., Deng, H.L., Fang, J.N., Dong, Q.: Isolation, purification and structural analysis of a polysaccharide MDG-1 from Ophiopogon japonicus. Acta. Pharmacol. Sin. 40, 636–639 (2005)

    CAS  Google Scholar 

  25. Whiteman, E.L., Cho, H., Birnbaum, M.J.: Role of Akt/protein kinase B in metabolism. Trends Endocrinol. Metab. 13, 444–451 (2002)

    Article  CAS  PubMed  Google Scholar 

  26. Zhu, M.Y., Mo, J.G., He, C.S., Xie, H.P., Ma, N., Wang, C.J.: Extraction, characterization of polysaccharides from lycium barbarum and its effect on bone gene expression in rats. Carbohydr. Polym. 80, 672–676 (2010)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by these projects in China (2012BAD33B04, 2012AA022108, 2012GB2A100016, IRT1166, 31000768, 31171731 and 10ZCZDSY07000).

Author information

Authors and Affiliations

  1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, People’s Republic of China

    Xiaolei Ma, Fuchuan Zhou, Yuanyuan Chen, Yuanyuan Zhang, Lihua Hou, Xiaohong Cao & Chunling Wang

Authors
  1. Xiaolei Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fuchuan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuanyuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuanyuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lihua Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaohong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chunling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chunling Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, X., Zhou, F., Chen, Y. et al. A polysaccharide from Grifola frondosa relieves insulin resistance of HepG2 cell by Akt-GSK-3 pathway. Glycoconj J 31, 355–363 (2014). https://doi.org/10.1007/s10719-014-9526-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-014-9526-x

Search

Navigation