Influence of food restriction and aging on the binding of insulin to liver nuclei in Fischer-344 rats

Aging is generally associated with the development of insulin resistance. Food restriction has been accepted as a powerful modulator of the aging process, though the underlying mechanisms are not yet elucidated. The present study was carried out to determine the effect of food restriction on the binding of insulin to liver nuclei of Fischer-344 rats ranging in age from 3-24 months. After isolating nuclei from livers of 3m, 6m, 10m, 12m and 24m ad libitum-fed and food-restricted rats, 100 μg of nuclear protein was incubated with 0.2 ng of ¹²⁵I-insulin and 0.2 to 2,000 ng/200 μl unlabeled insulin at 23°C for 2 hr. Scatchard analysis of the data revealed that insulin binding to nuclei was highest at 6m of age and an age-associated decline occurred in the binding of insulin to liver nuclei. The maximum number of binding sites for insulin in the liver nuclei of 3m, 6m, 10m and 24m old animals were 24±2, 37.5±2, 26±2.5, 14±3 for the ad libitum-fed group and 8.3±3, 38.5±2.5, 28.5±3, and 24.5±3 ng/mg protein for the food-restricted groups, respectively. The above data suggest that food restriction can delay the loss of insulin binding to liver nuclei. These observations suggest that food restriction may be an important modulator of insulin binding to liver nuclei which may have a functional role in delaying age-associated insulin resistance.