Structural characterization and antidiabetic potential of a novel heteropolysaccharide from Grifola frondosa via IRS1/PI3K-JNK signaling pathways

Carbohydr Polym. 2018 Oct 15:198:452-461. doi: 10.1016/j.carbpol.2018.06.077. Epub 2018 Jun 18.

Abstract

A novel heteropolysaccharide from Grifola frondosa named GFP-W has been isolated and purified by DEAE Sephadex A-52 chromatography. Gas chromatography, fourier transform infrared spectroscopy, one-dimensional (1H- and 13C-) and two-dimensional (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC) nuclear magnetic resonance spectroscopy were used to characterize its structure. The average molecular weight of GFP-W was 66.1 kDa. GFP-W mainly contained four kinds of linkage type units as β-D-GlcpA→, 1,2,6-α-Gal, →2)-α-Manp→, and →3)-α-L-Fucp-(1→. It could significantly increase the uptake of glucose in dexamethasone induced insulin resistant HepG2 cells by improving the mRNA and protein expression of insulin receptor substrate 1, phosphatidylinositol-3-kinase, and glucose transporter 4 upregulation and c-Jun N-terminal Kinase 1 downregulation. Moreover, antidiabetic activities of GFP-W were associated with significant changes in the extent of protein lysine acetylation, crotonylation, and succinylation levels. Our results provide a new hypoglycemic therapeutic role and an in-depth analysis on molecular mechanisms upon polysaccharides from G. frondosa.

Keywords: Antidiabetic; Grifola frondosa polysaccharide; Insulin signaling pathway; Protein lysine modification; Structural characterization.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Diabetes Mellitus, Experimental / drug therapy
  • Fungal Polysaccharides* / chemistry
  • Fungal Polysaccharides* / pharmacology
  • Fungal Polysaccharides* / therapeutic use
  • Glucose / metabolism
  • Grifola*
  • Hep G2 Cells
  • Humans
  • Hypoglycemic Agents* / chemistry
  • Hypoglycemic Agents* / pharmacology
  • Hypoglycemic Agents* / therapeutic use
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance
  • Male
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / drug effects

Substances

  • Fungal Polysaccharides
  • Hypoglycemic Agents
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Mitogen-Activated Protein Kinase 8
  • Glucose