Changes in insulin action and insulin secretion in the rat after dietary restriction early in life: influence of food restriction versus low-protein food restriction.

The effect of a limited period of undernutrition in young rats on insulin secretion and insulin action during adulthood has been studied. Four-week-old female rats were either food-restricted (35% restriction, 15% protein diet) or protein-calorie-restricted (35% restriction, 5% protein diet) for 4 weeks. Food-restricted rats gained weight at a lower rate than control rats. In the protein-calorie-restricted group, the alteration of weight gain was more severe. Basal plasma insulin was reduced only in protein-calorie-restricted rats. Glucose-stimulated insulin secretion (delta I) obtained in vivo after an intravenous glucose load was only moderately decreased in food-restricted group, whereas it was severely blunted in the protein-calorie-restricted group. In this last group, impairment of the insulin secretory response to glucose was related to an intrinsic impairment of beta-cell secretory capacity, since the insulin secretory response to glucose or arginine was decreased when tested in vitro (perfused pancreas). In food-restricted rats, basal plasma glucose level was kept normal, while a mild deterioration of glucose tolerance was detectable. This was related, of course, to the decrease of delta I as identified in vivo. However, data obtained under basal or euglycemic-hyperinsulinemic conditions provided direct evidence that insulin-mediated total glucose uptake (weight-related expression) was paradoxically enhanced. A similar conclusion was reached in protein-calorie-restricted rats; the increase of overall insulin-mediated glucose uptake was even more important. Such an adaptation, which was operating in both types of restriction, may help limit the deterioration of glucose tolerance in the face of impaired insulin release. In the basal postabsorptive state, the higher glucose utilization rate in both models originated from increased hepatic glucose production rates. During hyperinsulinemia, endogenous glucose production in food-restricted rats was normally blunted, but not in protein-calorie--restricted rats, thus indicating resistance of the hepatic glucose production pathway to insulin action in this group.