GSR and type 2 diabetes mellitus: In a study investigating the glutathione peroxidase 1 (GPX1) polymorphism in individuals with T2DM, GPX1 was found to possess a protective role in human endothelial cell dysfunction and atherosclerosis.469 GPX1 deficiency in diabetic ApoE-/- mice increases LDL oxidation and accelerates atherosclerosis.470 Ox-LDL restrains glutathione reductase (GR) activity and facilitates accumulating protein S-glutathionylation, ROS generation, and cell death in macrophages, promoting the development of atherosclerosis.471