Hypoglycemic Effect of Exopolysaccharide from Lactiplantibacillus plantarum JLAU103 on Streptozotocin and High-Fat Diet-Induced Type 2 Diabetic Mice

Two doses (300 mg/kg bw and 600 mg/kg bw) of the Lactiplantibacillus plantarum JLAU103 exopolysaccharide (EPS103) were orally administered to a type 2 diabetic (T2DM) mouse model induced by streptozotocin and a high-fat diet. The hypoglycemic, hypolipidemic and neuroprotective effects of EPS103 on T2DM mice were evaluated. The results indicated that administration of EPS103 could alleviate insulin resistance, reduce the levels of fasting blood glucose, glycosylated hemoglobin A1c, leptin and fasting serum insulin, improve glucose tolerance, protect pancreas and liver, and modulate blood lipid disorders. EPS103 promoted hepatic glycogen synthesis by upregulating the phosphorylation of GSK3β. Meanwhile, it upregulated the phosphorylation of IRS-1, PI3K and Akt, as well as the expression of IRS-2 and GLUT4, and downregulated the expression of PEPCK, G6Pase and PGC-1α, indicating that EPS103 promotes the uptake and transport of glucose and inhibits gluconeogenesis, which might be related to the activation of the IRS-1/PI3K/Akt pathway. Additionally, EPS103 can protect against brain nerve damage through improving oxidative stress injury, restoring the expression of IRS-2, alleviating neuronal apoptosis and inhibiting inflammation in the hippocampus of T2DM mice. Taken together, our results demonstrated that EPS103 may be a potential therapeutic agent for the treatment of T2DM.