Intriguingly, hyperglycemia-impaired agonist-induced NO release from endothelial cells in cultured human vascular endothelial cells [280], in mouse models of diabetes [281], and in human patients [279], although Orai1-mediated SOCE is the main responsible for the recruitment of the Ca2+/CaM-dependent eNOS [8]. The gene discussed is NOS3; the disease is diabetes mellitus.