Bifidobacterium longum TISTR 2893 Regulates Glycemic Homeostasis by Modulating the Hepatic Carbohydrate Metabolism in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats.

Accumulating evidence supports the beneficial effects of probiotics in regulating glucose and lipid metabolism; however, the underlying mechanisms of certain probiotic strains in diabetes remain unclear. The purpose of this study was to evaluate the anti-diabetic effects of Bifidobacterium longum TISTR 2893 in a high-fat diet (HFD)-induced type 2 diabetic (T2D) rat model, combined with a low dose of streptozotocin (STZ). Additionally, the B. longum TISTR 2893's effects on hepatic carbohydrate metabolism pathways were examined. The results demonstrated that B. longum TISTR 2893 treatment significantly suppressed fasting blood glucose (FBG) elevation and excessive water intake in the diabetic rats, while also enhancing glucose clearance following oral glucose loading. Moreover, B. longum TISTR 2893 improved pancreatic islet structure, which was associated with the suppression of pancreatic TNF-α and oxidative stress. Bifidobacterium longum TISTR 2893 also significantly alleviated diabetes-induced hepatic steatosis, as evidenced by reductions in hepatic triglyceride levels and Oil Red O staining intensity. Furthermore, B. longum TISTR 2893 modulated hepatic glucose metabolism by enhancing hexokinase activity, glycogen storage, and the expression of phospho-glycogen synthase kinase-3β (p-GSK-3β) and protein kinase B (AKT/PKB), while markedly inhibiting gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase-1 (PCK-1) expression and fructose-1,6-bisphosphatase (FBPase) activity. Additionally, B. longum TISTR 2893 exhibited antioxidant effects in the livers of the diabetic rats. In conclusion, these findings suggest that B. longum TISTR 2893 may exert hypoglycemic effects in T2D rats through the activation of AKT-mediated hepatic carbohydrate metabolism, which is linked to its antioxidative defense mechanisms.