GSR and Hyperglycemia: However, a chronic state of hyperglycemia and oxidative stress overloads the NRF2 defense mechanism: the activity of NRF2-associated antioxidant enzymes was reduced in in vitro models (HO-1 in animal diabetic models and SOD, glutathione reductase (GR), glutathione peroxidase (GPx) and catalase in diabetic patients).