Studies suggest that, in the early stages of atherosclerosis, insulin resistance may also contribute to the progression of atherosclerotic plaque formation by downregulating the insulin receptor–Akt1 signaling pathway, resulting in reduced activation of endothelial nitric oxide synthase (eNOS) and increased expression of vascular cell adhesion molecule-1 (VCAM-1) in arterial endothelial cells (30). The gene discussed is INSR; the disease is atherosclerosis.