Insulin injection in the fetal rat: accelerated intrauterine growth and altered fetal and neonatal glucose homeostasis.

Fetal hyperinsulinemia is a well-known correlate of accelerated fetal growth; the consequences of fetal hyperinsulinemia upon fetal and neonatal glucoregulation are less well understood. We injected rat fetuses of a litter on day 18 of gestation with either 5 units of long acting insulin (I) or 154 mmol/L NaCl. Twelve hours after injection, the wet and dry mass of total body and liver of I fetuses significantly exceeded that of controls. At birth (day 21.5), newborn I pups weighed 5.86 +/- .08 g, and controls, 5.48 +/- .05 g, (P less than .001). On day 18, within one hour of injection, fetal plasma insulin concentrations were significantly elevated and remained so for 24 hours. Mothers of I fetuses had significant elevations of plasma insulin at 1, 3, and 6 hours, and they developed transient hypoglycemia. Plasma glucose concentrations in I fetuses were significantly diminished at 1, 3, and 6 hours and then achieved control levels by 12 hours. Fetal hypoglycemia resulted from an apparent direct effect of insulin upon fetal tissue and from the maternal hypoglycemia. Hypoglycemic I fetuses demonstrated a sluggish alpha-cell response; they failed to increase plasma glucagon one hour after insulin injection. Values were significantly increased three hours after injection. At birth, I pups became hypoglycemic relative to controls. This was, in part, due to their significantly elevated plasma insulin concentrations at 120 and 240 minutes (120 minutes, 43.8 +/- 8 v 17.5 +/- 6 microU/mL, P less than .001). Plasma glucagon was significantly increased in I pups at 240 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)