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

David W. Boyle, Scott C. Denne, Helen Moorehead, Wei Hua Lee, Ronald R. Bowsher, Edward A. Liechty

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E1082-E1091
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume275
Issue number6 38-6
StatePublished - Dec 1 1998

Keywords

  • Amino acid kinetics
  • Glucose uptake
  • Hindlimb metabolism
  • Leucine
  • Oxygen uptake
  • Phenylalanine
  • Recombinant human insulin-like growth factor I

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry
  • Physiology (medical)

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