This chronic hyperinsulinemia exposes the vascular endothelium to a high-insulin environment for a prolonged period, downregulates the PI3K/Akt/eNOS signaling axis, reduces nitric oxide (NO) production, and simultaneously enhances the pro-inflammatory and adhesive functions of the endothelium, ultimately leading to vascular endothelial dysfunction—the initial link in the development of atherosclerosis (27). Here, INS is linked to atherosclerosis.