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
1998 American Journal of Physiology. Endocrinology and Metabolism  
Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E1082-E1091, 1998.-Insulinlike 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,
more » ... ized, 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 Ϯ 0.13 before vs. 0.73 Ϯ 0.19 µmol/min during IGF-I) or breakdown (phenylalanine rate of appearance 0.67 Ϯ 0.13 before vs. 0.60 Ϯ 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 Ϯ 3.3 to 37.6 Ϯ 2.7 µmol/min) as did fetal leucine oxidation (8.4 Ϯ 0.8 to 6.8 Ϯ 0.6 µmol/min). There was no change in the umbilical uptake of leucine, and although not statistically significant, fetal leucine accretion increased 2.4fold. These results provide further evidence that IGF-I promotes fetal protein accretion; however, its site of action is in tissues other than skeletal muscle.
doi:10.1152/ajpendo.1998.275.6.e1082 fatcat:rjm3i472bbc4bnepr6mby2d57q