Hypoglycemic effects of Lactiplantibacillus plantarum B19 via promoting AMPK/PI3K/AKT signaling pathway

Abstract

Lactic acid bacteria (LAB) are noted for their effectiveness as an adjunctive treatment in managing disorders related to glucose metabolism. Type 2 diabetes mellitus, a significant contributor to numerous chronic health issues, is tightly linked to insulin resistance (IR). This study aimed to screen LAB strains with hypoglycemic ability, assess their probiotic characteristics, and research their in vitro hypoglycemic mechanism based on IR model in HepG2 cells (IR-HepG2). Out of 73 LAB strains derived from traditional Chinese fermented food, Lactiplantibacillus plantarum B19 was chosen due to its superior probiotic attributes, safety profile, and an α-glucosidase inhibition rate surpassing 60 %. The cell-free supernatant of B19 (B19-CFS) was subjected to further in vitro analysis in IR-HepG2 cells. In comparison to the model group, the high concentration of B19-CFS (0.5 mg/mL) treatment group increased glucose consumption and glycogen content by 184.41 % and 44.10 %, respectively. Meanwhile, the content of glutathione increased by 102.34 %, while that of malondialdehyde decreased by 42.86 %. For the activities of superoxide dismutase and glutathione peroxidase, they increased by 33.95 % and 43.04 % respectively, while the activity of glutathione reductase decreased by 46.67 %. These effects were comparable to those observed with 1 mM metformin. Further examination through RT-qPCR revealed B19-CFS treatment could regulate the mRNA expression related to AMPK/PI3K/AKT pathway. The results indicated that B19-CFS mitigated hepatic IR by activating the AMPK/PI3K/AKT signaling pathway, promoting glycolysis while suppressing glycogen synthesis and oxidative stress. In conclusion, L. plantarum B19 is a potential therapeutic probiotic for lowering glucose.