PeroxiredoxinI deficiency increases pancreatic β‑cell apoptosis after streptozotocin stimulation via the AKT/GSK3β signaling pathway.

Abstract

Apoptosis of pancreatic β-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 β-cell apoptosis is not completely understood. In the present study, the role of peroxiredoxin 1 (Prx I) during streptozotocin (STZ)-induced apoptosis of pancreatic β-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)-3β phosphorylation significantly decreased following Prx I knockdown in MIN6 cells. However, phosphorylated β-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 β-cell death in vivo and in vitro by regulating the AKT/GSK-3β/β-catenin signaling pathway, as well as NF-κB signaling. These findings provide a theoretical basis for treatment of pancreatic damage.