The activation of nNOS and eNOS depends on Ca2+ and calmodulin (CaM), and small amount of NO can be generated under normal circumstances; iNOS is a non-calcium-dependent enzyme with little or no expression under normal conditions, however, factors including hyperglycemia, AGEs, oxidative stress, ischemia, and hypoxia etc. can activate the enzyme and induce a large amount of NO production. The gene discussed is NOS1; the disease is Hyperglycemia.