Our group previously demonstrated that overexpression of selenium-dependent glutathione peroxidase-1 (GPX1) in mice (OE) led to escalated glucose-stimulated insulin secretion and hyperinsulinemia.
The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine.
Overproduction of the major antioxidant enzyme, glutathione peroxidase 1, caused seemingly beneficial changes in pancreatic PDX1 and UCP2, but eventually led to chronic hyperinsulinaemia by dysregulating islet insulin production and secretion.