Mechanism of Antihyperglycemic Activity of Extracellular Polysaccharopeptides from Fermented Turkey Tail Medicinal Mushroom Trametes versicolor (Agaricomycetes) in Type 2 Diabetic Rats

The antihyperglycemic activity of extracellular polysaccharopeptides (ePSP) obtained from Trametes versicolor (TV) strain LH-1 has been demonstrated in hepatic cells and diabetic animals. This study further investigated the mechanisms of T. versicolor-ePSP on regulating glucose metabolism, including insulin signaling molecules and glucose metabolism-associated enzymes, in the liver of rats with type 2 diabetes mellitus (T2DM). Male Wistar rats, fed with a high-fat diet followed by a streptozotocin injection to induce T2DM, were orally administered water or T. versicolor-ePSP at doses of 0.1, 0.5, or 1.0 g/kg/d. After 4 weeks of T. versicolor-ePSP administration, T2DM rats exhibited significantly lower postprandial blood glucose levels, decreased liver triglyceride and cholesterol contents, and improved serum liver function indices in a dose-dependent manner (P < 0.05, one-way ANOVA). Additionally, T2DM rats administered T. versicolor-ePSP had significantly activated insulin receptors and decreased proteins involved in insulin signaling pathway, such as insulin receptor substrates, PI3K, and total and activated Akt, and AMP-activated protein kinase in the liver. T. versicolor-ePSP administration, especially at 1.0 g/kg per day, significantly increased glucose transporters in the cell membrane and decreased glucokinase and glucose-6-phosphotase in the cytosol of the liver. In conclusion, the antihyperglycemic activities of T. versicolor-ePSP may be associated with enhanced hepatic function, alleviated gluconeogenesis, and facilitated glucose transport in an insulin- and AMPK-independent manner in the liver of T2DM rats.