Fetal hyperinsulinemia and protein turnover in fetal rat tissues.

The effects of fetal hyperinsulinemia on protein turnover in various tissues of fetal rats were determined after transuteral injection of insulin to rat fetuses at day 19 of gestation. Tissue protein content was measured on the subsequent days of gestation (days 20-22), and protein synthesis was determined at day 20 of gestation in fetal tissues after intravenous injection of [3H]phenylalanine into the maternal circulation, followed by measurements of tissue free and protein-bound phenylalanine specific radioactivity in fetal diaphragm, brain, heart, and liver. Rates of protein degradation in these fetal tissues were calculated by subtracting protein accretion rates from rates of protein synthesis. The injection of insulin to rat fetuses at day 19 of gestation resulted in relative macrosomia versus saline-injected controls from the same litter (body wt at day 20 of gestation, 3.26 +/- 0.15 g for saline-injected fetuses and 3.60 +/- 0.25 g for insulin-injected fetuses, P less than 0.001) and increased protein and RNA content of brain, heart, and liver. Although fractional rates of protein synthesis were not significantly elevated in tissues from the hyperinsulinemic fetuses, absolute rates of protein synthesis were increased in brain, heart, and liver of hyperinsulinemic fetuses. Hyperinsulinemia did not reduce calculated rates of protein breakdown in fetal brain, heart, or liver but did in fetal diaphragm. We conclude that the major effect of fetal hyperinsulinemia on protein turnover in rats is to increase protein synthesis in selected tissues without simultaneously affecting protein breakdown.

Fetal rat islet insulin deficiency following maternal administration of streptozotocin.

Pancreatic islets were isolated from the fetuses of normal rats and rats made diabetic by the iv administration of streptozotocin (STZ) on either Day 3 or 5 of pregnancy. Of the rats made diabetic on Day 3, one group also received insulin injections at the appearance of glucosuria. Maternal blood glucose on Day 20 of gestation was significantly different in the diabetic rats (405 +/- 27 mg/dl) from the normal (97 +/- 1 mg/dl) and insulin-treated diabetic rats (69 +/- 9 mg/dl). While fetal weight was significantly decreased in the STZ-treated rats (2.64 +/- 0.13 g vs 3.52 +/- 0.05 g for the control group, P less than 0.005), fetal glucose was significantly higher in the STZ-treated than in normal pups (342 +/- 11 vs 35 +/- 1 mg/dl, P less than 0.005). Both fetal weight and glucose were normalized by insulin treatment: 3.16 +/- 0.18 g and 31 +/- 7 mg/dl, respectively. Insulin release from fetal islets of diabetic dams was blunted after a week in culture both in basal and stimulated conditions. After 2 weeks in culture, there was partial recovery in the insulin response to glucose but it did not equal to that measured in fetal islets from the normal and insulin-treated diabetic rats. These data suggest maternal hyperglycemia severely impairs fetal weight and insulin release from fetal rat islets in vitro, and correction of the hyperglycemia by insulin treatment not only improves fetal weight and glucose concentrations, but it also normalizes insulin release from fetal rat islets in vitro.