It has been shown that glucose tolerance and insulin resistance are altered by the aging process. Glucose tolerance tends to decline with age while insulin resistance increases. In prior studies I have been able to demonstrate that daily excercise in 9 and 30 month old animals could improve glucose tolerance and increase insulin sensitivity. However, the response of these rats was well below that of younger 3 month old sedentary control animals. Therefore, the age related changes that produce the decline in cellular function would appear to begin before 9 months of age. It has been shown recently that age-related changes in insulin sensitivity may be due to decreased glucose uptake by skeletal muscle, and occur before 4 months of age. It was shown that the decline in glucose utilization appears to be related to muscle glycogen metabolism and may be induced by weight gain and not age. The purpose of this investigation will be to determine the effects of weight reduction, through exercise and food restriction, in rats under going the rapid period of growth that occurs prior to 4 months of age. Animals will be sacrificed at 1.5 and 4 months of age. The 4 month old rats will be separated into exercise-trained (activity wheels), Pairfed (weight matched to trained) and sedentary controls. Insulin stimulated glucose uptake will be measured using hindlimb perfusion techniques. Glycogen metabolism will be examined in a separate group of animals by analyzing glycogen, glycogen synthase, and glycogen phosphorylase in selected muscles of the hindlimb. In addition other parameters such as food intake, growth and blood chemistry will be monitored. The data will provide needed information concerning the development of insulin resistance with age, and will indicate how daily exercise and weight gain influences the process.
