Aging and Insulin Resistance: Just Say iNOS

The ubiquitous presence of insulin resistancecannot be understated. First brought to light byHimsworth and Kerr (1) in 1939, insulin re-sistance, defined as a subnormal response to a given dose of insulin, was ushered into prime time by Gerald Reaven (2), where it has remained at center stage. Insulin resistance is a major feature of type 2 diabetes (2). Insulin resistance is also associated with obesity, essential hypertension, dyslipidemia, nonalcoholic fatty liver disease, obstructive sleep apnea, and cancer (3). This cluster of maladies has been termed by Reaven as the “insulin resistance syndrome. ” Therefore, an individual with in-sulin resistance is strongly predisposed to an increased risk of life-threatening clinical conditions, including cardiovas-cular disease. As Reaven points out, the clinical consequences of insulin resistance are not due to insulin resistance per se but come from the hyperinsulinemia that occurs as the individual with