Glutathione peroxidase-1 (GPX1) is the first identified selenoprotein and selenoperoxidase in mammals. We have reported that overexpression of GPX1 in mice induces type-2-like diabetes phenotypes, including hyperinsulinemia (McClung et al. 2004, Wang et al. 2008). In searching for the underlying mechanism for these phenotypes, we have discovered a diminished expression of regenerating islet-derived protein 2 (REG2) in pancreatic islets of the GPX1 over-expressing (OE) mice (Yun et al. 2019). This study was performed to test if and how GPX1 suppressed Reg2 expression via scavenging reactive oxygen species (ROS).