Peripheral metabolism of insulin, proinsulin, and C-peptide in the pregnant rat.

Abstract

AB ST R A CT To clarify alterations in carbohydrate metabolismI whllich occuir in pregnancy, metabolic clearance rates of insulin, proinsulin, and C-peptide were measured by the constant infusion technique in term-pregnant rats and in virgin littermates. In addition, placental permeability to these peptides was evaluated by simultaneous determination of their conicentration in fetal blood, amniiotic fluid, and maternal arterial blood, and the renal extraction and excretion of insulin and C-peptide were determined duiring simuitiltaneotus studies of renal hemodynamics.The metabolic clearance rate (MICR) of insulin was higher (P <0.005) in pregnant animals (61.5±+1.7 ml/ min per kg nonconceptus body weiglht) than in virgin littermates (51.5±2.2 ml/nmin per kg). Insulin disappearance from the circulatioin after both single injection and discontinuance of a coinstant infusion Nas also faster in gravid animals. In contrast, the AICR of proinsulin and C-peptide, anid the disappearance of C-peptide from the circulation were siimilar in pregnanlt and cointrol rats. The placenta was virtually impermiieable to each of the three polypeptides since their mean levels in both fetal blood and amniotic fluid did not exceed 2.5 ng/ml and were only minimally iinflueinced by pharmacological concentrations as high as 60 ng,jml in the maternal circula- These results indicate that the peripheral metabolism of insulini is accelerated in pregnancy, while that of proinsulin and C-peptide is unaffected. Since transplacenital passage of insulin is negligible and its renal clearanice is not increased, the enhanced MCR of insulin in pregnancy is due to increased metabolism at an extrarenal site probably within the placenta itself.

Kinetics of human connecting peptide in normal and diabetic subjects.

“…This also applies to insulin-treated diabetics in whom exogenous insulin as well as endogenous insulin antibodies interfere with the measurement of endogenous insulin (13). In animals (15)(16)(17) as well as in humans (18,19), the turn-over of C-peptide is slower than that of insulin. However, detailed studies concerning the kinetics of C-peptide turnover have not been carried out in normal man.…”

Prenatal dehydration alters renin–angiotensin system associated with angiotensin-increased blood pressure in young offspring

“…The placenta is impermeable to polypeptides and protein hormones. 32,33 Thus, an increase in fetal hormones was independent of the maternal side. New findings of this study include the following: first, the substrate angiotensinogen in the fetal liver, the main source in peripheral systems for the precursor of Ang II, was significantly increased by maternal dehydration; second, an increase in fetal plasma Ang I indicated that either production of angiotensinogen or activity of a key enzyme renin in the fetus was enhanced; and third, the major bioactive peptide of the RAS-Ang II in the fetal circulation was markedly increased following maternal water deprivation.…”

Development of a Radioimmunoassay for Plasma C-Peptide in Sheep: Kinetics of C-Peptide and Effects of Exogenous Growth Hormone and Glucose on Insulin and C-Peptide

“…On the other hand, it has been shown that there is negligible hepatic extraction of C-peptide in rats (Stoll et al 1970), normal dogs (Polonsky et al 1983) and dogs given oral glucose . Furthermore, the clearance of C-peptide has been found to be constant under a wide range of physiological conditions and at varying concentrations of plasma C-peptide in rats (Katz et al 1975), dogs (Polonsky et al 1983; and humans (Faber et al 1979).…”