Effects of Gestational Age, Birth and Feeding on the Insulinogenic Response to Glucose and Tolbutamide by Fetal and Newborn Rat Pancreas

Sodoyez-Goffaux, F; Sodoyez, Jean-Claude; Foà, Piero P.

doi:10.2337/diab.20.9.586

Cited by 47 publications

(29 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relatively high rate of biosynthesis, accompanied by a relatively low pancreatic insulin content and by relatively high levels of circulating hormone, characteristic of the rat fetus, are consistent with the observations of other workers (5,13,63) and suggest that the insulin turnover is faster in the fetus than in the suckling animal. On the other hand, if one calculates the ratio of the amount of insulin secreted by pancreatic islets isolated from animals of different ages and incubated in buffer containing glucose at concentrations of 30 and 300 mgjlOO ml, one observes (Table 1) a rather symmetrical developmental pattern which indicates that relatively more insulin is secreted at low glucose concentration at an age when glucose tolerance is impaired.…”

Section: Discussionsupporting

confidence: 90%

“…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 insulin (IRI) reaches values that are higher than those found in the dam (2,13,26,42,63). A significant decrease in fetal serum IRI occurs on the last day of intrauterine life (14), at the time when the level of glucagon and, consequently, the glucagon to insulin ratio, increase markedly (14, 15, 3 l ) , possibly explaining why the mammalian neonate does not tolerate a glucose load as well as the adult animal (49,64).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 1975

View full text Add to dashboard Cite

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 ...

show abstract

Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

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

et al. 1975

View full text Add to dashboard Cite

show abstract

“…explants (7), pancreatic pieces (8,9), or isolated fetal (10) or neonatal (11) islets had been used supported the conclusion that glucose was not an insulinogenic agent before term. Other experiments suggested that the fetal B cells were not entirely glucose blind because phosphodiesterase inhibitors unmasked (10) or markedly enhanced (12) the secretagogue effect of glucose, and glucose alone was found capable of stimulating insulin biosynthesis (13).…”

Section: Methodsmentioning

confidence: 91%

Insulin Secretion and Metabolism during the Perinatal Period in the Rat

Sodoyez-Goffaux¹,

Sodoyez²,

Vos³

1979

J. Clin. Invest.

View full text Add to dashboard Cite

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

show abstract

“…This is of great physiological interest since in the 3-day-old rat pancreas regulation of insulin biosynthesis and release occurs in a period of islet and beta cell growth (54) and functional differentiation. Indeed, insulin content on the 3rd (55) day after birth rises to twice the insulin content of the 1st day of life (55). In this respect two points are noteworthy.…”

mentioning

confidence: 87%

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

García¹,

Jarrousse²,

Rosselin³

1976

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of "I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro)insulin in this system. In all conditions tested, the incorporation of [8H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM cose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca"+ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucoseinduced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 ,M) and tolbutamide (400 ELM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [8H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas.These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMPinduced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has

show abstract

Effects of Gestational Age, Birth and Feeding on the Insulinogenic Response to Glucose and Tolbutamide by Fetal and Newborn Rat Pancreas

Cited by 47 publications

References 9 publications

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

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

Insulin Secretion and Metabolism during the Perinatal Period in the Rat

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

Contact Info

Product

Resources

About