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Tolbutamide infused into the chronically catheterized sheep fetus produced significant secretion of insulin. An optimal dose range of 100-200 mg/kg estimated fetal weight was demonstrated. Paired tolbutamide and glucose infusions using a square wave technique demonstrated that although early phase insulin secretion is dimished in the fetus, this is not due to an absolute deficiency of stored insulin. Tolbutamide produced peak insulin concentrations of 51.6 +/- 9.0 muu/ml by 20 min postinfusion in the fetus. When similar tolbutamide infusions were performed in neonatal lambs, qualitatively similar insulin response curves were demonstrated although peak insulin levels were much greater (260 +/- 70 muu/ml at 20 min). A fall in plasma glucose was demonstrated in both fetal and neonatal lambs (to 75 and 39% of control values, respectively) by 60 min after tolbutamide infusion. In the fetus, this fall was not associated with changes in maternal glucose concentration.

Response of the Fetal and Newborn Lamb to Glucose and Tolbutamide Infusions