Postmaturity in the rat: impairment of insulin, glucagon, and glycogen stores

Prolonged gestation (2 extra days in utero) was obtained by daily subcutaneous injection of progesterone (2.5 mg) to pregnant rats from day 20.5 post coitum (p.c.) throughout day 22.5 p.c. after reduction of the litter to 6 fetuses on day 14.5 p.c. Exogenous progesterone per se or litter reduction were without effect of fetal pancreas or fetal liver. Plasma insulin, insulin and glucagon in the pancreas, and liver glycogen stores have been systematically measured in postmature animals and in controls during the perinatal period. In 23.5 day-old postmature as compared to 21.5 day-old normal fetuses, the intrauterine mortality was increased (26%), the body weight was increased by 30%, the liver weight was decreased by 20%, the glycogen content of liver was dramatically depleted (1.1 +/- 0.2 mg/g body weight on day 23.5 p.c. against 6.7 +/- 0.3 on day 21.5 p.c.), the plasma insulin was lowered by 63% and the blood glucose level was normal. In postmature neonates during the first day of life the mortality rate was considerable (40%) and a dramatic fall of blood glucose was observed 6 hours after birth. The accumulation of insulin and glucagon in the pancreas, which normally occurs in the two first days after birth, was much lower in the postmature fetuses: in 23.5 day-old fetuses as compared to 2 day-old normal newborns of the same gestational age the insulin content was only 50% and the glucagon content 69%. The deficit of insulin accumulation in the postmature pancreas lasted at least five days. The ability of the endocrine pancreas to recover from this alteration as well shown by the lack of diabetes when the animals were examined three weeks later by a glucose tolerance test. These findings suggest that the drop of plasma insulin is a prime factor in causing the lack of glycogen stores in prolonged fetuses and the impairement of glycogen stores appear to be an important feature of postmaturity, since neonates exhibit, in these conditions, a lethal drop of blood glucose as glycogenolysis operates on very low glycogen stores.