Vitexin restores pancreatic β-cell function and insulin signaling through Nrf2 and NF-κB signaling pathways.

Chronic hyperglycemia induces pancreatic β-cell dysfunction through several cell signaling pathways. The β-cell loss by apoptosis appears to play a crucial role in the onset and progression of diabetes. This study was aimed to investigate the role of vitexin against high glucose-induced β-cells apoptosis and the underlying mechanisms involved therein. INS-1 cells were pretreated with vitexin (20 and 40 μM) followed by high glucose (33 mM) exposure and the cytotoxicity was assessed by MTT. The effect of vitexin on nuclear factor erythroid 2-related factor 2 (Nrf2) and NF-kB signaling molecules have been studied. Vitexin-mediated stimulation of Nrf2 was assessed. Vitexin protected the cells against high glucose toxicity in a concentration-dependent manner. Vitexin improved insulin signaling as analyzed by the levels of functional proteins in the insulin pathways, viz., insulin receptor (IR), insulin receptor substrate (IRS)-1 and IRS-2, glucose transporter -2, and glucose-stimulated insulin secretion. Vitexin improved the high glucose-induced nuclear transcription factor system by suppressing Rel A, Rel B, P50/p105, and IκB expression resulting in decreased cell apoptosis, further confirmed by the reduction in the percentage of Annexin-V positive cells. Our data suggest that vitexin improves insulin secretion by activating key proteins, including NF-κB and Nrf2 in β-cells regulating apoptosis.