A study has explored the vascular cytoprotective effects of HO-1 against hyperglycemia-induced oxidative stress in experimental diabetes and found that vascular extracellular SOD and plasma catalase activities were significantly reduced in diabetic rats compared with nondiabetic rats and that upregulation of HO-1 expression by administration of CoPP caused a large increase in extracellular SOD levels [62]. This evidence concerns the gene SOD1 and diabetes mellitus.