Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep
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 feta...
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Published in | American journal of physiology: endocrinology and metabolism Vol. 275; no. 6; pp. E1082 - E1091 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.12.1998
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Subjects | |
Online Access | Get full text |
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Summary: | 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 |
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ISSN: | 0193-1849 0002-9513 1522-1555 |
DOI: | 10.1152/ajpendo.1998.275.6.e1082 |