Effects of insulin on ovine fetal leucine kinetics and protein metabolism

Abstract

Fetuses of eight pregnant ewes (114-117 d of gestation) were used to study whether fetal insulin concentration affects fetal protein accretion and, if so, whether such changes are caused by effects on protein synthesis or protein breakdown. Fetal leucine kinetics were measured by infusion of [1-14C]leucine during each of three protocols: (I) low vs. normal insulin concentration; (II) low vs. high insulin concentration; and (III) low vs. high insulin concentration during amino acid infusion to keep leucine concentration constant. Fetal leucine concentration (233 +/- 20 vs. 195 +/- 18 microM) and clearance (48.3 +/- 4.4 vs. 54.2 +/- 5.5 ml/kg per min) were the only aspects of fetal leucine kinetics that changed during protocol I. During protocol II, insulin infusion decreased fetal leucine concentration (222 +/- 22 vs. 175 +/- 22), decreased fetal leucine disposal (11.63 +/- 0.89 vs. 12.55 +/- 0.89 mumol/kg per min), increased leucine clearance (48.0 +/- 4.2 vs. 57.6 +/- 6.5 ml/kg per min), decreased leucine decarboxylation (1.77 +/- 0.17 vs. 2.04 +/- 0.21 mumol/kg per min), decreased nonoxidative leucine disposal (9.81 +/- 0.78 vs. 10.51 +/- 0.74 mumol/kg per min), decreased release of leucine from fetal protein (7.43 +/- 1.08 vs. 8.38 +/- 0.84 mumol/kg per min), but did not change the accretion of leucine into protein. In contrast, when leucine concentrations (205 +/- 25 vs. 189 +/- 23) were maintained (protocol III), insulin infusion did not change fetal leucine disposal, decarboxylation, or nonoxidative disposal although leucine clearance still rose (55.4 +/- 5.0 vs. 64.4 +/- 5.9 ml/kg/min). Fetal release of leucine from protein, however, decreased (7.46 +/- 0.83 vs. 8.57 +/- 0.71 mumol/kg per min) and the accretion of leucine into protein increased (3.27 +/- 0.30 vs. 1.80 +/- 0.32 mumol/kg/min). These findings show that insulin decreases fetal protein breakdown. If insulin-induced hypoaminoacidemia occurs, protein synthesis decreases so that no net accretion of protein occurs. If fetal amino acid concentrations are maintained, however, insulin itself does not affect protein synthesis, and fetal protein accretion increases.