Effects of circulating IGF-I on glucose and amino acid kinetics in the ovine fetus

To investigate the role of insulin-like growth factor I (IGF-I) in the regulation of fetal metabolism, the kinetics of leucine, phenylalanine, and glucose were assessed in the chronically catheterized ovine fetus (0.85 gestation) before and during infusion of recombinant human IGF-I (rhIGF-I). Substrate kinetics were determined by tracer dilution. rhIGF-I was infused at 6.7 nmol . kg fetus(-1). h(-1). Fetal insulin and growth hormone concentrations were significantly decreased by 50% during rhIGF-I infusion. Net umbilical glucose uptake was unchanged, and glucose rate of appearance increased in the fed state only. There were no changes in the net umbilical uptakes of leucine or phenylalanine, but the rates of appearance of both declined during rhIGF-I infusion, indicative of decreased fetal protein breakdown (R(a,Leu) 45.4 +/- 1.40 to 40 +/- 1.4 mu mol/min in the fed state, 43 +/- 1.5 to 37 +/- 1.5 mu mol/min in the fasted state; R(a,Phe) 10.7 +/- 0.3 to 10.4 +/- 0.3 mu mol/min in the fed state and from 10.7 +/- 0.3 to 9.8 +/- 0.3 mu mol/min in the fasted state). Leucine oxidation was also decreased (8.90 +/- 0.76 to 6.52 +/- 0.81 mu mol/min, P = 0.025), more so in the fasted than the fed state. These results indicate a significant antiproteolytic endocrine effect for IGF-I in the late-gestation mammalian fetus.