Dw. Boyle et al., Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep, AM J P-ENDO, 38(6), 1998, pp. E1082-E1091
Citations number
50
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Insulin-like growth factor I (IGF-I) has been shown to have significant ana
bolic 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 wi
th the effects at the whole body level before and during a 3-h infusion of
rhIGF-I into the external iliac artery at 150 mu g/h. Infusion of rhIGF-I r
esulted in increases in IGF-I concentrations by 2- to 5.75-fold in the ipsi
lateral iliac vein and by nearly 3-fold in the abdominal aorta. In the stud
y limb, IGF-I had no effect on protein synthesis (phenylalanine rate of dis
posal 0.88 +/- 0.13 before vs. 0.73 +/- 0.19 mu mol/min during IGF-I) or br
eakdown (phenylalanine rate of appearance 0.67 +/- 0.13 before vs. 0.60 +/-
0.17 mu mol/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 f
etal protein breakdown, decreased during IGF-I infusion (rate of appearance
of leucine 41.1 +/- 3.3 to 37.6 +/- 2.7 mu mol/min) as did fetal leucine o
xidation (8.4 +/- 0.8 to 6.8 +/- 0.6 mu mol/min). There was no change in th
e umbilical uptake of leucine, and although not statistically significant,
fetal leucine accretion increased 2.4-fold. These results provide further e
vidence that IGF-I promotes fetal protein accretion; however, its site of a
ction is in tissues other than skeletal muscle.