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

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.