Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep.
Insulin-like growth factor I (IGF-I) has been shown to have significant anabolic effects in the regulation of fetal protein metabolism. To investigate the tissue-specific effects of IGF-I on fetal skeletal muscle metabolism, we infused recombinant human (rh) IGF-I directly into the hindlimb of nine chronically catheterized, late-gestation fetal sheep. Substrate balance and amino acid kinetics were measured across the hindlimb and were compared with the effects at the whole body level before and during a 3-h infusion of rhIGF-I into the external iliac artery at 150 microgram/h. Infusion of rhIGF-I resulted in increases in IGF-I concentrations by 2- to 5. 75-fold in the ipsilateral iliac vein and by nearly 3-fold in the abdominal aorta. In the study limb, IGF-I had no effect on protein synthesis (phenylalanine rate of disposal 0.88 +/- 0.13 before vs. 0. 73 +/- 0.19 micromol/min during IGF-I) or breakdown (phenylalanine rate of appearance 0.67 +/- 0.13 before vs. 0.60 +/- 0.17 micromol/min during IGF-I) and did not alter net phenylalanine balance. IGF-I also did not affect hindlimb oxygen or glucose uptake. In contrast, at the whole body level, the rate of appearance of leucine, indicative of fetal protein breakdown, decreased during IGF-I infusion (rate of appearance of leucine 41.1 +/- 3.3 to 37.6 +/- 2.7 micromol/min) as did fetal leucine oxidation (8.4 +/- 0.8 to 6.8 +/- 0.6 micromol/min). There was no change in the umbilical uptake of leucine, and although not statistically significant, fetal leucine accretion increased 2.4-fold. These results provide further evidence that IGF-I promotes fetal protein accretion; however, its site of action is in tissues other than skeletal muscle.
Boyle
D W
DW
Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5119, USA.
Denne
S C
SC
Moorehead
H
H
Lee
W H
WH
Bowsher
R R
RR
Liechty
E A
EA
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005333:Fetus / Q000378:metabolism*; D006614:Hindlimb; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000493:pharmacokinetics; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010649:Phenylalanine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins; D012756:Sheep / Q000196:embryology
D000596:Amino Acids; D009124:Muscle Proteins; D011506:Proteins; D011994:Recombinant Proteins; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D007930:Leucine