Peroxiredoxin I Deficiency Increases Pancreatic Beta-Cell Apoptosis After Streptozotocin Stimulation Via The Akt/Gsk3 Beta Signaling Pathway

Apoptosis of pancreatic beta-cells is involved in the pathogenesis of type I and II diabetes. Peroxiredoxin I (Prx I) serves an important role in regulating cellular apoptosis; however, the role of Prx I in pancreatic beta-cell apoptosis is not completely understood. In the present study, the role of peroxiredoxin 1 (Prx I) during streptozotocin (STZ)-induced apoptosis of pancreatic beta-cells was investigated. The expression level of Prx I was decreased by STZ treatment in a time-dependent manner, and apoptosis of Prx I knockdown MIN6 cells was increased by STZ stimulation, compared with untransduced MIN6 cells. Furthermore, an intraperitoneal injection of STZ increased pancreatic islet damage in Prx I knockout mice, compared with wild-type and Prx II knockout mice. AKT and glycogen synthase kinase (GSK)-3 beta phosphorylation significantly decreased following Prx I knockdown in MIN6 cells. However, phosphorylated beta-catenin and p65 levels significantly increased after STZ stimulation, compared with untransduced cells. The results of the present study indicate that deletion of Prx I mediated STZ-induced pancreatic beta-cell death in vivo and in vitro by regulating the AKT/GSK-3 beta/beta-catenin signaling pathway, as well as NF-kappa B signaling. These findings provide a theoretical basis for treatment of pancreatic damage.