INS and atherosclerosis: The PI3K-AKT-endothelial nitric oxide synthase (eNOS) signaling pathway is central to transducing both mechanical stretch (Hu et al., 2013) and hormonal inputs (insulin) to regulate eNOS expression and activity, which, in turn, regulates vasodilation (blood flow and pressure), inhibits leukocyte aggregation, and limits proliferation of vascular smooth muscle cells (atherosclerosis).