The purpose of the present study was to investigate the influence of nutrients and insulin on IGFs and their binding proteins (IGFBPs) during the fetal and neonatal periods of three rat populations: (a) rats undernourished by a 35% reduction in the diet from day 16 of gestation, (b) streptozotocin-induced diabetic rats from the same day, or 4 days after birth, and (c) control rats. Fetuses from the diabetic population showed a decrease in insulinemia at 19 and 21 days, along with an increase in glycemia at all stages. Neither glycemia nor insulinemia changed in the fetuses of undernourished mothers, but body weight was decreased at birth. Serum IGF-II decreased at 18 and 19 days of gestation in fetuses from undernourished mother, and increased at 18, 19 and 21 days in fetuses from diabetic mothers. Serum IGFBPs of low molecular weight (IGFBP-1 and IGFBP-2) increased in the three fetal populations studied, although no changes in serum IGFBPs were found from the effect of undernutrition or diabetes, but fetal liver IGFBP-1 mRNA expression was found to decreased in undernourished and diabetic animals as compared with controls. In neonatal rats, body weight, insulinemia and serum GH decreased in both undernourished and diabetic rats vs controls, while glycemia decreased in the undernourished and increased in the diabetic group. Serum IGF-II decreased only in diabetic rats and serum IGF-I decreased in both groups. The neonatal serum 30 kDa complex (IGFBP-1 and -2) also increased in undernutrition and diabetes parallel to the expression of mRNA. But, taken together, the changes in IGFBP peptide levels and liver mRNA expression strongly suggest that the 30 kDa complex seems to be composed mostly of IGFBP-1 in the diabetic group and of both IGFBP-1 and -2 in the undernourished animals. The studies of liver mRNA expression of IGFs and IGFBPs confirm the different metabolic control mechanism for the availability of IGFs by the IGFBPs, depending on the animal's maturity. The different adaptation shown by the diabetic neonatal population was confirmed by correlation studies between body weight, glycemia, insulinemia, IGF-I and IGFBPs. The different mechanism of adaptation in diabetic vs undernourished rats seems to be probably due to the decisive role played by hyperglycemia in the diabetic population, and also shows the crucial influence of nutritional status on IGFs and IGFBPs.
Glucose tolerance and insulin effects on glucose production and utilization by various tissues were studied in 70-day-old anesthetized rats submitted to food restriction from the fetal stage. Basal and glucose-induced plasma insulin levels were reduced in food-restricted rats without alterations in glucose tolerance. Insulin action was quantified by using the euglycemic-hyperinsulinemic clamp technique. Glucose turnover rates were measured by using D-[6-3H]glucose. Exogenous insulin failed to decrease glucose production in food-restricted rats. Weight-related whole body glucose utilization was higher in restricted rats than in controls both in the basal (21.9 +/- 0.7 vs. 9.4 +/- 0.6 mg.min-1.kg-1) and hyperinsulinemic states (37.5 +/- 1.1 vs. 14.0 +/- 1.2 mg.min-1.kg-1). Local glucose utilization by peripheral tissues was estimated by a 2-deoxy-D-[1-3H]glucose technique. In both basal and hyperinsulinemic conditions glucose utilization was increased in various adipose and muscle tissues of the food-restricted rats as compared with the controls. Thus we conclude that food restriction leads to an increase in the insulin-mediated glucose uptake by various peripheral tissues and to insulin resistance in the liver.
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