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

Abstract

To clarify alterations in carbohydrate metabolism which occur 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 concentration in fetal blood, amniotic fluid, and maternal arterial blood, and the renal extraction and excretion of insulin and C peptide were determined during simultaneous studies of renal hemodynamics. The metabolic clearance rate (MCR) of insulin was higher (P < 0.005) in pregnant animals (61.5 ± 1.7 ml/min per kg nonconceptus body wt) than in virgin littermates (51.5 ± 2.2 ml/min per kg). Insulin disappearance from the circulation after both single injection and discontinuance of a constant infusion was also faster in gravid animals. In contrast, the MCR of proinsulin and C peptide, and the disappearance of C peptide from the circulation were similar in pregnant and control rats. The placenta was virtually impermeable to each of the 3 polypeptides since their mean levels in both fetal blood and amniotic fluid did not exceed 2.5 ng/ml and were only minimally influenced by pharmacological concentrations as high as 60 ng/ml in the maternal circulation. The renal clearance of insulin (renal arteriovenous insulin difference x renal plasma flow) was lower, and its contribution to insulin MCR was less in pregnant animals than in controls (19.4 ± 1.5% vs. 28.7 ± 3.7%, P < 0.05), whereas the renal clearance and renal clearance/MCR of C peptide were similar in pregnant rats and virgin littermates.