NOS3 and diabetes mellitus: In the diabetes-related HG model, upregulated ARG1 induced eNOS uncoupling through the sequential activation of RhoA/Rho kinase (ROCK) and p38 mitogen-activated protein kinases (p38 MAPK) in mouse aortic and bovine aortic endothelial cells (BAECs), contributing to the development of diabetes/hyperglycemia-induced vascular endothelial dysfunction [106, 107] (Figure 2).