Anthocyanins from Chinese bayberry extract activate transcription factor Nrf2 in β cells and negatively regulate oxidative stress-induced autophagy.

Islet replacement is a promising cure for insulin-dependent diabetes but is limited by a massive early cell death following transplantation. Overburden oxidative stress is one of the major factors causing cell damage. We have shown previously that anthocyanins in Chinese bayberry extract protected β cells (INS-1) from hydrogen peroxide (H₂O₂)-induced apoptosis and decreased grafts' apoptosis after transplantation partially through heme oxygenase-1 (HO-1) up-regulation. In the present study, we observed that H₂O₂ stimulation induced autophagy in β cells. Inhibition of autophagy increased cell viability and decreased cell death. Anthocyanin pretreatment attenuated oxidative stress-mediated autophagic cell death. Anthocyanins activated antioxidant transcription factor Nrf2 in INS-1 cells, and Nrf2/HO-1 negatively regulated autophagy process. Furthermore, we here demonstrate that autophagy also took place in β cell grafts during the early post-transplantation phase. β Cells pretreated with anthocyanins displayed decreased extent of autophagy after transplantation. Taken together, these findings further supported the conclusion that anthocyanins could serve as a protective agent of β cells and suggested that autophagy might play a role in β cells during transplantation.