The structures of two polysaccharides from Fructus Corni and their protective effect on insulin resistance.

Type 2 diabetes mellitus (T2DM) is characterized by impaired cellular or organ responsiveness to insulin, which results in ineffective glucose disposal and lacks a definitive treatment. Previous studies suggest that polysaccharides hold promise as natural agents for the prevention and treatment of T2DM. In this study, we identified two polysaccharides from Fructus Corni, PFC-CI and PFC-CII, with molecular weights of 59.0 kDa and 26.0 kDa, respectively. PFC-CI consists of T-α-Galp-(1→6)-α-Galp-(1→6)-α-Galp-(1→[4)-GalpA-(1→4)-GalpA-OMe-(1→4)-α-GalpA-3-OAc-(1→]→[2)-Rhap-(1→4)-α-GalpA-(1→], with side chains composed of α-Araf-(1→, →3)-α-Araf-(1→, →3,5)-α-Araf-(1→, →5)-α-Araf-(1→. PFC-CII is a linear α-1,6-glucan. Among them, PFC-CI showed superior effects on promoting glucose consumption and uptake in insulin-resistant (IR) HepG2 cells. In vivo, PFC-CI significantly alleviate IR in high-fat diet and streptozotocin-induced diabetic rats, indicating its potential as a therapeutic agent for T2DM. Mechanistically, PFC-CI modulates the glucose transporter 2 (Glut2)/glucokinase signaling pathway, thereby exerting anti-T2DM effects. This research indicates that Fructus Corni contains a potential therapeutic polysaccharide as a specific regulator of Glut2 for treating T2DM.