Effect of hyperinsulinemia on ovine fetal leucine kinetics during prolonged maternal fasting

The primary effect of insulin on whole body protein metabolism in postnatal life is to reduce proteolysis. To assess the role of insulin in the regulation of protein metabolism in prenatal life, leucine kinetics were determined in the ovine fetus at baseline and in response to hyperinsulinemia. These measurements were made in each fetus in two different maternal states: ad libitum maternal feeding and after a 5-day maternal fast. Maternal fasting resulted in significant increases in baseline fetal leucine rate of appearance (Ra; 51.9 +/- 16.7 vs. 37.3 +/- 3.6 mumol/min, P < 0.05) and leucine oxidation (30.1 +/- 8.9 vs. 8.8 +/- 2.2 mumol/min, P < 0.05). Hyperinsulinemia, which was associated with significant increases in fetal glucose utilization, did not affect total fetal leucine R(a) or leucine release from fetal proteolysis in either maternal state. Under well-fed maternal conditions, hyperinsulinemia produced no changes in the fetal oxidative or nonoxidative disposal of leucine. In contrast, during maternal fasting, hyperinsulinemia reduced fetal leucine oxidation (11.0 +/- 3.7 vs. 31.1 +/- 8.9 mumol/min, P < 0.05) and increased the nonoxidative disposal of leucine (35.4 +/- 4.0 vs. 19.0 +/- 6.1 mumol/min, P < 0.05). This resulted in a change in the fetal leucine accretion rate from negative to positive (-20.9 +/- 7.5 vs. 7.5 +/- 6.7 mumol/min, P < 0.05). These results suggest that, under conditions of restricted maternal substrate intake, fetal hyperinsulinemia and the attendant increase in fetal glucose utilization are associated with increased protein synthesis rather than decreased protein breakdown, thereby improving fetal leucine carcass accretion.