Exendin-4 prevented pancreatic beta cells from apoptosis in (Type I) diabetic mouse via keap1-Nrf2 signaling

摘要

Type I diabetes mellitus (TIDM) serves as a large contributor to morbidity as well as mortality globally with persistently elevating prevalence. It is known that oxidative damage by free radicals participates in etiology, complications, as well as progression of TIDM. In our research, we demonstrate that Keap1-Nrf2-ARE pathway was stimulated by exendin-4 treatment during the development of type I diabetes in murine TIDM model as well as in pancreatic β-cells. We also observed excessive reactive oxygen species (ROS) production, low level of cell death, and PKC phosphorylation on exendine-4 treatment. Nrf2 knockdown led to suppression of ROS generation as well as increasing apoptosis. Moreover, siRNA-mediated Nrf2 down-regulation attenuated the suppressive effect of exendin-4 in pancreatic β-cell viability, through modulating apoptosis promoting- and counteracting-proteins, Bax, and Bcl-2. Thus, the present study indicates exendin-4 mediates activation of Keap1-Nrf2-ARE pathway and may serve as a promising agent to treat TIDM.