Effect of insulin on uptake of metabolic substrates by the sheep fetus

Abstract

To measure the effect of fetal hyperinsulinemia on fetal oxidative metabolic rate and the uptake of fetal oxidative substrates, we operated on 12 near-term ewes under spinal anesthesia and placed catheters in the fetus under local anesthesia. Four days after surgery, we began an 18-h insulin infusion, at the end of which we drew blood samples for analysis of oxygen, glucose, lactate, amino-nitrogen concentrations, blood gases, pH, hematocrit, and plasma insulin concentrations, then injected radiolabeled microspheres to measure umbilical blood flow. Three to five infusions were given to each fetus. Fetal plasma insulin concentrations varied from 0.3 to 60 microU/ml. As fetal plasma insulin concentration rose, the blood concentrations of oxygen, glucose, lactate, and amino-nitrogen fell, but the fetal uptakes of oxygen, glucose, and amino-nitrogen rose. The rise of fetal oxygen uptake occurred by increasing oxygen extraction, resulting in arterial hypoxemia. The increase of the glucose uptake was sufficient to account for an increased fraction of oxidative metabolism, allowing the increased uptake of amino acids to be used for either synthetic or oxidative purposes.

Effects of insulin on ovine fetal leucine kinetics and protein metabolism.

“…As expected, fetal oxygen content fell during insulin infusion, an effect we All data are means±SEM. Significance * at P < 0.05; * at P < 0.005; § at P < 0.00 1. and others have noted previously (31,32). We also noted a mild respiratory acidosis during insulin infusion (protocols II and III), a finding also noted during other studies of fetal hyperinsulinemia (32).…”

“…Indeed, fetal amino acid nitrogen uptake significantly increases during hypoglycemic hyperinsulinemia (31 ). Estimates ofnormal fetal leucine uptake have ranged from 3.7 to 4.7 Atm/kg per min ( 12,14,27,29,40), values that agree with the control measurements of this study.…”

Iron Deficiency Alters Auditory Recognition Memory in Newborn Infants of Diabetic Mothers

“…The degree of iron deficiency in the newborn IDM is also a function of poor maternal glycemic control and to the degree of fetal hypoxia and augmented erythropoiesis (5). Studies in fetal sheep demonstrate that fetal hyperglycemia with its attendant hyperinsulinemia results in an increased fetal metabolic rate (51,52) and increased oxygen demand with a compensatory increase in the red cell mass (53)(54)(55). The latter increases the utilization of iron and in severe cases causes depletion of tissue iron initially from liver, heart, and finally the brain as available fetal iron is shifted into the red cell mass (6,18).…”

The Effect of Prolonged Intrauterine Hyperinsulinemia on Iron Utilization in Fetal Sheep

“…We speculate that the driving force for the increased red cell iron utilization seen in our fetal sheep was the accelerated Hb synthesis associated with the significant decrease in arterial oxygen saturation. Chronic fetal hyperinsulinemia causes arterial oxygen desaturation (8,16), most likely by increasing fetal oxygen consumption (8). Hyperinsulinemia increases fetal erythropoiesis in rhesus monkeys, most likely in response to hypoxemia (6), although hyperinsulinemia may also independently stimulate erythropoiesis (1 7).…”