Effects of Age and Obesity on Insulin Binding to Isolated Adipocytes1212

UNLABELLED: We have measured insulin binding to isolated adipocytes prepared from rats of varying ages and body weights. The ability of adipocytes to bind insulin progressively decreases as animals get older and fatter until about 70 days of age and 300 g body weight are reached. From this point on further decreases in insulin binding to adipocytes were not seen as rats got older and fatter. Analysis of the data indicated that this decrease in insulin binding could be accounted for by decreased numbers of insulin receptor sites per cell. Further studies were conducted in which animals were allowed to age, but obesity was prevented or reversed by hypocaloric diets. In these experiments decreased insulin binding was either prevented or restored to normal by the negative caloric state, indicating that age had no appreciable effect on the ability of adipocytes to bind insulin. The influence of the obesity associated variables-hyperinsulinemia and increased fat cell size-on insulin binding was also examined. These latter studies are consistent with the concept that elevated in vivo plasma insulin levels lead to decreased insulin receptors, and further suggest a role for additonal factors in regulating the adipocyte insulin receptor. IN CONCLUSION: 1. Decreased insulin binding to adipocytes is closely related to the obese state. 2. This decrease in insulin binding can be accounted for by decreased numbers of receptor sites per cell, and 3. The mecahnism(s) underlying this decreased insulin binding are complex and probably represents an effect of more than one variable.