Insulin Secretion and Metabolism during the Perinatal Period in the Rat

Abstract

A B S T R A C T To better understand why plasma immunoreactive insulin (IRI) concentration is high in the rat fetus during the last 3 d of gestation and why fetal hyperinsulinemia abruptly subsides after birth, insulin secretion and metabolic clearance rates were estimated in fetuses and nursed pups.Intravenously injected ['251]monoiodoinsulin was cleared from the plasma of prematurely delivered pups at least as rapidly as from that of 7-to 10-d-old pups, suggesting that fetal hyperinsulinemia is not a result of slow clearance of the hormone. The fetal liver bound 35% of the injected label within 3 min, and binding was saturable. The uptake of radioactivity by *the fetal kidney was nonsaturable and much lower than that of adult rat kidney.Isolated fetal islets were already reactive to glucose on the 19th d of gestation. Pancreatic insulin secretory capacity was estimated by measuring (a) the insulin release of isolated islets incubated in the presence of 2.8 mM glucose, (b) the insulin content of the same islets, and (c) the total insulin extracted from the pancreas, using the formula (a x c)lb. 2 d before birth, the pancreatic insulin secretory capacity was high, accounting for fetal hyperinsulinemia. It was even higher after birth, not accounting for the postnatal decrease in plasma IRI concentration.Pups delivered by caesarian section 1 d before term exhibited a brisk decrease in plasma IRI concentration when the cord was cut. By contrast, if the feto-placental unit was removed from the dam, maintaining fetal Parts of this work were presented at The 13th Annual

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

“…In the control rats, the plasma insulin level at the end of fetal life was found to be very high as compared to those in newborn and adult rats in accordance with previous studies [14][15][16]. Concerning the plasma glucagon level, it reached its highest value during neonatal life when compared to the fetal and adult age, in confirmation of previous reports [14,17].…”

Insulin Receptors in the Fetal Rat Lung. A Transient Characteristic of Fetal Cells?

“…Indeed, the fetal liver slowly expelled 1251-~yr, as evidenced by the sluggish decrease of total liver radioactivity over the period studied. In addition, in more mature fetuses, we have previously reported that the plasma concentration of IZ5I-Tyr Ins degradation products increased very slowly with time (17).…”

“…Based on this approach, several fetal organs, notably the liver and kidneys, appeared to concentrate insulin throughout the studied period of gestation. Insulin binding in the liver was inhibited by coinjection of 100 m u unlabeled insulin (saturable binding), whereas insulin uptake by the kidneys was not (unsaturable uptake) (16,17,18). The lungs appeared to concentrate significantly the labeled hormone in only the youngest fetuses.…”

Reduced Plasma Somatomedin Activity and Costal Cartilage Sulfate Incorporation Activity during Experimental Growth Retardation in the Fetal Rat

“…As each fetus was exposed, a deep incision was made in the axillary region and blood was collected on ice while the placenta and umbilicus were still intact. The latter point is of importance since blood glucose and insulin values can alter rapidly in the rat fetus especially following severance of the umbilical cord (13). Blood from all animals within a single uterine horn, either ligated or control, was pooled before the centrifugation and separation of plasma which was stored at -20" C. After noting the position of each fetus within the uterus, they were weighed to an accuracy of 1 mg and the nose-tail length was measured by ruler to the nearest millimeter.…”