Fig. 4

Hyperinsulinemia, insulin resistance, and cardiovascular disease. High insulin concentrations in the blood may occur due to genetic predisposition, overnutrition, or high-dose insulin treatment of type 2 diabetes. Hyperinsulinemia induces “insulin resistance” as a defense response to maintain glucose homeostasis. Conversely, insulin resistance may be directly induced such as by growth hormone or pro-inflammatory cytokines. Hyperinsulinemia and insulin resistance enhance the risk of cardiovascular disease, by inducing endothelial dysfunction, suppression of endothelial nitric oxide synthase (eNOS), and activation and promotion of calcium ion influx into smooth muscle cells, resulting in increased vascular tone, enhanced reabsorption of sodium ions in renal tubules, adhesion of macrophages to the vessel wall, and development of arterial lesions with increased lipoprotein lipase activity and cardiovascular disease