Insulin resistance is typically defined as a reduced ability of insulin to induce glucose uptake by target tissues such as fat and skeletal muscle cells. It accompanies several disease states, including obesity, type 2 diabetes, hepatitis C, and polycystic ovary syndrome, and is a primary feature of metabolic syndrome. Outside of its effects on blood glucose levels, insulin resistance is also associated with a 2- to 3-fold increased risk of cardiovascular mortality. In 1996, Alain Baron, Helmut Steinberg, and colleagues demonstrated that insulin resistance is associated with endothelial dysfunction. This seminal observation led to significant advances in our understanding of insulin’s action in health and disease.
Kieren J. Mather, Helmut O. Steinberg, Alain D. Baron
Distinct signaling pathways mediate insulin effects on nitric oxide and endothelin in vascular endothelial cells.
Endothelial insulin resistance can preferentially impair signaling via the IRS/PI3K pathway, adversely affecting the balance between prothrombotic and antithrombotic signaling. This imbalance could potentially contribute to the increased cardiovascular mortality associated with insulin resistance.