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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume275
Issue number6 38-6
StatePublished - 1998

Fingerprint

Muscle Proteins
Insulin-Like Growth Factor I
Metabolism
Sheep
Skeletal Muscle
Leucine
Fetal Proteins
Hindlimb
Phenylalanine
Muscle
Tissue
Iliac Vein
Umbilicus
Anabolic Agents
Iliac Artery
Abdominal Aorta
Extremities
Oxygen
Amino Acids
Glucose

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)

Cite this

Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep. / Boyle, David; Denne, Scott; Moorehead, Helen; Lee, Wei Hua; Bowsher, Ronald R.; Liechty, Edward A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 275, No. 6 38-6, 1998.

Research output: Contribution to journalArticle

@article{2e5e7c2194994c6992fe1f09cc2f9c3f,
title = "Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep",
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.",
keywords = "Amino acid kinetics, Glucose uptake, Hindlimb metabolism, Leucine, Oxygen uptake, Phenylalanine, Recombinant human insulin-like growth factor I",
author = "David Boyle and Scott Denne and Helen Moorehead and Lee, {Wei Hua} and Bowsher, {Ronald R.} and Liechty, {Edward A.}",
year = "1998",
language = "English",
volume = "275",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "6 38-6",

}

TY - JOUR

T1 - Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep

AU - Boyle, David

AU - Denne, Scott

AU - Moorehead, Helen

AU - Lee, Wei Hua

AU - Bowsher, Ronald R.

AU - Liechty, Edward A.

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - Amino acid kinetics

KW - Glucose uptake

KW - Hindlimb metabolism

KW - Leucine

KW - Oxygen uptake

KW - Phenylalanine

KW - Recombinant human insulin-like growth factor I

UR - http://www.scopus.com/inward/record.url?scp=0032444896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032444896&partnerID=8YFLogxK

M3 - Article

C2 - 9843752

AN - SCOPUS:0032444896

VL - 275

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 6 38-6

ER -