The Synthesis and Release of Insulin in Fetal, Nursing and Young Adult Rats: Studies in Vivo and in Vitro

Extract: The secretion of insulin in vivo and its synthesis and release by pancreatic islets in vitro were studied in rats at various stages of development. An oral glucose load caused a rapid and significant increase in the serum insulin level of pregnant rats and a slower response in their 21-day-old fetuses. Circulating free fatty acids (FFA) decreased in the dams, but did not change in the fetuses. A relative glucose intolerance was found in pups 1 hr, 5 days, and 10 days after birth. This was accompanied by delayed insulin response and by little or no decrease of circulating FFA. After weaning, the glucose tolerance and the insulin and FFA responses gradually improved. The oral administration of a 10-amino acid mixture caused a greater insulin release in newborn and nursing rats than in 21-day-old fetuses or in young adult rats. Total serum lipids were higher in 1-, 5-, 10-, and 20-day-old rats than in fetuses and adult animals, whether fed or fasted, but 18 hr of fasting decreased total lipids and phospholipids in all age groups. Thus, the age of relative hyperlipidemia corresponded with that of relative glucose intolerance. The secretion of insulin in vitro by pancreatic islets of 5-, 10-, 20-, 30-, and 45-day-old rats increased significantly when the concentration of glucose in the incubation medium was increased from 30 to 300 mg/ml. The islets of 30- and 45-day-old rats secreted the largest amount of insulin. The insulin content of pancreatic islets was higher and the percentage of insulin secreted in relation to the hormonal content was smaller in the islets of nursing rats. Islets of fetal, nursing, and adult rats incorporated L-[4,5-3H] leucine into proinsulin and insulin, but the conversion of proinsulin to insulin was minimal in the 1-day-old rat. This incorporation was greater when the glucose concentration of the medium or the incubation time were increased. Thus, birth appears to be associated with a temporary decrease in the ability to release insulin and to dispose of an exogenous glucose load.Speculation: Birth deprives the newborn pup of transplacental nutrition and exposes it to the danger of neonatal hypoglycemia, especially in the interval between birth and the first act of nursing. This danger is moderated by a previously described increase in the serum level of glucagon and by a decrease in the serum level of insulin. This change in the glucagon to insulin ratio favors hepatic glycogenolysis and gluconeogenesis and, possibly aided by the relative hyperlipidemia characteristic of this age, decreases the utilization of glucose by the relatively large masses of insulin-responsive tissues. Gluconeogenesis continues to be a major source of glucose throughout the nursing age, when the animal consumes a diet rich in protein and fat and low in carbohydrate. Although the fetal pancreas can synthesize insulin, the mechanism for its release and hence the ability to dispose of a glucose load do not reach full maturity until weaning, when the dietary intake of carbohydrate increases and the level of serum lipids decreases toward the values characteristic of the adult animal.