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 beta 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 beta 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 beta cell grafts during the early post-transplantation phase. beta 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 beta cells and suggested that autophagy might play a role in beta cells during transplantation.