Selenium-Enriched Cordyceps militaris Polysaccharides Alleviate Insulin Resistance in HepG2 Cells by Regulating the PI3K/AKT/GLUT4 Signaling Pathway.

Metal ion-rich Cordyceps militaris polysaccharides (CMP) are obtained by biotransformation and chemical synthesis. The physicochemical properties and bioactivity of selenium-enriched CMP (Se-CMP) obtained using biotransformation remain unclear. Here, selenium nanoparticles were used to produce Se-CMP. Total sugars, molecular weight, monosaccharide composition, and galacturonic acid and Se contents of Se-CMP and CMP were determined. The Se content of Se-CMP was 5.11 ± 0.81 μg/g. The Se-CMP is composed of glucosamine hydrochloride, xylose, arabinose, galactose, mannose, and glucose in a molar ratio of 0.001: 0.036: 0.022: 0.133: 0.150: 0.659. Se-CMP was structurally characterized using Fourier transform infrared spectroscopy and circular dichroism spectroscopy. Se-CMP inhibited α-glucosidase activity (half-maximal inhibitory concentration 0.474 mg/mL). Se-CMP also increased glucose uptake and glycogen synthesis in insulin-resistant HepG2 cells by activating the PI3K/AKT/GLUT4 signaling pathway. It also effectively reduced the level of reactive oxygen species in insulin-resistant HepG2 cells while increasing the activity of antioxidant enzymes, including catalase, glutathione peroxidase, and superoxide dismutase, reducing oxidative damage. Se-CMP has significantly alleviated insulin-resistant properties and may be a natural anti-IR source for managing Type II diabetes mellitus.