Fetal leucine oxidation rate is elevated during fasting of the ewe. Euglycemic hyperinsulinemia causes the leucine oxidation rate to decline. However, it is unclear whether this is a direct effect of insulin or is secondary to increased insulin-mediated glucose utilization. To better delineate the mechanism of decreased oxidation, we suppressed fetal insulin secretion by somatostatin infusion. Glucose was infused at a variable rate to achieve glucose concentrations 125 and 150% of basal. Leucine rate of appearance (Ra) was determined by infusion of [15N, 1-13C]leucine. Fraction of leucine appearance oxidized was determined by [1-14C]leucine infusion and determination of fetal 14CO2 excretion. Each fetus was studied during ad libitum maternal feeding and after a 5-day complete maternal fast. Changes were noted in fetal leucine oxidation, which declined from 8.4 +/- 1.2 to 5.0 +/- 0.8 mumol/min in the fed state during glucose infusion. Basal leucine oxidation was elevated during fasting (11 +/- 1.5 mumol/min, P < 0.05) and declined to 8.0 +/- 1.4 mumol/min during glucose infusion (P = 0.056). Leucine carbon Ra was unchanged by fasting and by glucose infusion; leucine nitrogen Ra declined in the fed state only. Leucine oxidation was inversely correlated with glucose concentration (oxidation = 12-0.26 x glucose concentration, r = 0.42, P = 0.004). Leucine oxidation was not correlated with insulin concentration (r = 0.2). Changes in fetal glucose concentration may alter the pattern of utilization of essential amino acids, independent of changes in insulin and insulin-mediated glucose utilization rate.