Aging Enhances the Insulin Resistance in Obesity through both Receptor and Postreceptor Alterations*

The association between aging and insulin resistance is well recognized. To clarify possible mechanisms, both the binding and the action of insulin were studied in abdominal sc fat cells from two groups of obese nondiabetic women matched for relative weight and fasting insulin levels. The age ranges of the two groups were 16-37 (mean, 28) and 47-77 (mean, 61) yr, respectively. Insulin binding was significantly decreased in the elderly (approximately 40%; P less than 0.05), which Scatchard analysis showed to be due to a decreased number of binding sites. In accordance with the binding data, the dose-response curve for insulin's stimulatory effect on glucose incorporation into triglycerides was shifted to the right. Glucose incorporation in the absence of insulin was similar in both groups, whereas the increment induced by a maximally stimulating concentration of insulin was reduced in the elderly (approximately 50%; P less than 0.02), suggesting the presence of a postreceptor defect. A negative correlation was found between insulin response and age. Thus, in the presence of obesity, aging is associated with resistance to the stimulatory effect of insulin on glucose metabolism in adipocytes. The insulin resistance is due to both receptor and postreceptor perturbations.