Structural characterization and insulin resistance-improving activity of glucomannogalactan from Volvariella volvacea

The polysaccharide VVPI-3a (21.8 kDa) from Volvariella volvacea was isolated and identified, and its insulin resistance-improving activity was evaluated in insulin-resistant HepG2 (IR-HepG2) cells. VVPI-3a is composed of unsubstituted residues including →6)-α-D-Galp-(1→, →6)-α-D-(3-O-Me)-Galp-(1→, →2)-β-D-Galp-(1→, →6)-β-D-Galp-(1→ and →6)-β-D-(3-O-Me)-Galp-(1→. It also contains monosubstituted residues including (→2,6)-α-D-Manp-(1→ and →2,6)-α-D-(4-O-Ac)-Manp-(1→). Its backbone contains alternating →6)-Galp-(1→ and →2,6)-Manp-(1→ residues. Branching occurs at O-2 of mannose, where terminal glucosyl units are attached. The conformation of VVPI-3a was further confirmed by Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD) and Congo red analysis, indicating that it is a neutral polysaccharide with pores and projections on a uniformly distributed surface. In the glucosamine-induced insulin-resistant HepG2 cell model of HepG2 cells, VVPI-3a (0.25-1 mg/mL) significantly enhances glucose uptake in IR-HepG2 cells. VVPI-3a may improve glucose uptake by increasing the mRNA transcription of GLUT4, thereby enhancing insulin sensitivity in IR-HepG2 cells and inhibiting the key enzymes G6pase and PEPCK. These findings contribute to the growing body of research on the polysaccharides of Volvariella volvacea and their roles in insulin resistance-improving activity.