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 insu lin secretion and insulin action during adulthood has been studied. Fo ur-week-old female rats were either food-restricted (35% restriction, 15% protein diet) or protein-calorie-restricted (35% restriction, 5% p rotein diet) for 4 weeks. Food-restricted rats gained weight at a lowe r rate than control rats. In the protein-calorie-restricted group, the alteration of weight gain was more severe. Basal plasma insulin was r educed only in protein-calorie-restricted rats. Glucose-stimulated ins ulin 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 th is last group, impairment of the insulin secretory response to glucose was related to an intrinsic impairment of beta-cell secretory capacit y, since the insulin secretory response to glucose or arginine was dec reased when tested in vitro (perfused pancreas). In food-restricted ra ts, basal plasma glucose level was kept normal, while a mild deteriora tion of glucose tolerance was detectable. This was related, of course, to the decrease of Delta I as identified in vivo. However, data obtai ned under basal or euglycemic-hyperinsulinemic conditions provided dir ect evidence that insulin-mediated total glucose uptake (weight-relate d expression) was paradoxically enhanced. A similar conclusion was rea ched in protein-calorie-restricted rats; the increase of overall insul in-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 re lease. In the basal postabsorptive state, the higher glucose utilizati on rate in both models originated from increased hepatic glucose produ ction 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 pr oduction pathway to insulin action in this group. Copyright (C) 1995 b y W.B. Saunders Company