Increased fetal glucose concentration decreases ovine fetal leucine oxidation independent of insulin

Abstract

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.