Does Insulin Work as Good One or Bad One for the Cardiovascular Tissues?

Insulin tends to focus on its metabolic effects, especially its effects on glucose and lipid metabolism. In fact, in diabetes, in which insulin action failure is the pathology, the main symptom is hyperglycemia and its treatment aims to improve glucose and lipid metabolism. However, because epidemiological studies have revealed that hyperinsulinemia is a risk factor for cardiovascular disease, independent of blood glucose and lipid level (1), research has also focused on insulin's effects other than its effects on glucose and lipid metabolism. For example, insulin is known to enhance the reabsorption of Na+ as an effect on renal tubules (2), and in fact, is known that urinary excretion of Na+ is reduced in hypertensive patients with insulin resistance. It is assumed that hyperinsulinemia is involved in the pathophysiology of hypertension through an increase in circulating plasma volume via enhanced Na+ reabsorption in the kidney. On the other hand, it has been revealed that insulin's effects on vascular tissues are directly activated by PI3-kinase/AKT in vascular endothelial cells, leading to activation by phosphorylation of endothelial nitric oxide synthase (3), and thus to enhanced nitric oxide production and increased blood flow (4). Thus, insulin action has been considered to act vascularly protective through activation of vascular endothelium, particularly activation of endothelial nitric oxide synthase. On the other hand, as already mentioned, epidemiologically, hyperinsulinemia is a risk factor for cardiovascular diseases, and it has been pointed out that hyperinsulinemia may be a cardiovascular risk factor through factors related to insulin resistance that cause hyperinsulinemia, such as transient hyperglycemia, dyslipidemia, and hypertension.