Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep

• Published in: American journal of physiology: endocrinology and metabolism Vol. 275; no. 6; pp. E1082 - E1091
• Main Authors: Boyle, David W, Denne, Scott C, Moorehead, Helen, Lee, Wei-Hua, Bowsher, Ronald R, Liechty, Edward A
• Format: Journal Article
• Language: English
• Published: United States 01.12.1998
• Subjects: Amino Acids - metabolism; Animals; Fetus - metabolism; Hindlimb; Humans; Insulin-Like Growth Factor I - pharmacology; Kinetics; Leucine - pharmacokinetics; Muscle Proteins - metabolism; Muscle, Skeletal - embryology; Oxidation-Reduction - drug effects; Phenylalanine - metabolism; Proteins - metabolism; Recombinant Proteins; Sheep - embryology
• ISSN: 0193-1849; 0002-9513; 1522-1555
• DOI: 10.1152/ajpendo.1998.275.6.e1082

1  Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine and 2  Eli Lilly Research Laboratories, Indianapolis, Indiana 46202-5119 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 µg/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 µmol/min during IGF-I) or breakdown (phenylalanine rate of appearance 0.67 ± 0.13 before vs. 0.60 ± 0.17 µmol/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 µmol/min) as did fetal leucine oxidation (8.4 ± 0.8 to 6.8 ± 0.6 µmol/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. phenylalanine; leucine; amino acid kinetics; hindlimb metabolism; glucose uptake; oxygen uptake; recombinant human insulin-like growth factor I