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

Abstract

ExtractThe 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 inyoung adult rats. Total serum lipids were higher in I-, 5-, lo-, 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-, lo-, 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 ,~-~~] l e u c i n e 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 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 I the values characteristic of the adult animal. 1The synthesis and storage of insulin in the pancreatic B cells of the rat appear to start during the 1 l t h day of gestation (36, 59). However, the precise time at which the insulin-releasing mechanism begins to function has not been determined and may vary with the nature of the stimulus. Thus, the fetal pancreas, even though insensitive to glucose (4, SO), may respond to other substances (see Reference 37) so that, toward the end of pregnancy, the fetal serum ...

Effect of Triamcinolone on Renal and Hepatic Phosphoenolpyruvate Carboxykinase in the Newborn Rat

“…The effective induction of liver P-pyruvate carboxykinase in the newborn rat is henceforth readily understandable, when the unique state of insulin regulation during neonatal period is considered. The sluggish reactivity of the pancreatic fl cells to glucose loading [6,7], the persistently low levels of serum insulin from birth to the third week of life [7], and the decreased sensitivity of tissues to insulin during this period allow for an expression of the effects of glucocorticoids. Thus, under these conditions, triamcinolone was able to increase P-pyruvate carboxykinase equally well in the liver and kidney of neonatal rats (Fig.…”

“…During the perinatal period, plasma insulin sharply declines and remains at a low level over the first two postnatal weeks [7,8]. Injection of insulin in utero prior to birth prevents the subsequent emergence of P-pyruvate carboxykinase [3].…”

Response of the Fetal and Newborn Lamb to Glucose and Tolbutamide Infusions

“…In the adult, secretion of insulin in response to a constant glucose stimulus occurs in a biphasic mode with early and late peaks (8). Recently, Blazquez et al (3) and Philipps et al (23) have shown an absence or diminution in the early phase of insulin secretion in response to fetal glucose elevation. Yet the newborn lamb and other species of newborns exhibit relatively brisk biphasic insulin responses during glucose infusion shortly after birth (1, 18).…”

“…Serial infusions were performed only after a recovery period of at least 48 hr after the last infusion. Plasma arterial samples for glucose and insulin were obtained twice in the 30 min preceding infusion and then at I%, 3,5,10,20,30,60,90, and 120 rnin postinfusion. Maternal arterial glucose and insulin samples were obtained during the control period and at 30, 60, and 120 min postinfusion to assess possible changes in maternal homeostasis.…”

Ontogeny of MAP Kinases in Rat Small Intestine: Premature Stimulation by Insulin of BBM Hydrolases Is Regulated by ERKs but not by p-38 MAP Kinase

“…The onset of weaning (d 14 -17) in the suckling rat is a critical period during which immature enterocytes exhibit elevated responsiveness to insulin (1). At this time, plasma insulin levels rise markedly (2), whereas milk-borne insulin is still active (3), allowing optimal interaction of the hormone with intestinal IR, which are located on both endoluminal and basolateral membranes of the cell (4). After weaning, the 2-fold decrease in IR concentration is associated with a reduction in responsiveness of mature enterocytes to the hormone (1,5).…”