Protein anabolic effects of insulin and IGF-I in the ovine fetus.
We determined the effect of insulin and/or recombinant human (rh)IGF-I infusion on ovine fetal phenylalanine kinetics, protein synthesis, and phenylalanine accretion. The chronically catheterized fetal lamb model was used at 130 days gestation. All studies were performed while fetal glucose and amino acid concentrations were held constant. Experimental infusates were 1). saline, 2). rhIGF-I plus a replacement dose of insulin (40 nmol), 3). insulin (890 mIU/h), and 4). IGF-I plus insulin (40 nmol IGF-I/h and 890 mIU insulin/h). Both hormones increased glucose and amino acid utilization, with insulin having a greater effect. The major effect on phenylalanine kinetics was a pronounced fall in phenylalanine hydroxylation, again with insulin having the greatest effect. Whole body protein breakdown was not significantly altered by either hormone; whole body protein synthesis was significantly increased during the combined infusion. Protein accretion was increased by both hormones, with the greatest increase during combined infusion. The fractional synthetic rate (FSR) of circulating albumin was increased by IGF-I but not by insulin. Both hormones significantly increased skeletal muscle FSR without a synergistic effect. The anabolic effects of insulin and IGF-I were more pronounced in these studies than in previous studies where amino acid concentrations were not maintained. The present data also suggest that insulin and IGF-I promote fetal growth through distinct, organ-specific mechanisms.
Shen
Weihua
W
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Wisniowski
Paul
P
Ahmed
Lasker
L
Boyle
David W
DW
Denne
Scott C
SC
Liechty
Edward A
EA
D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000493:pharmacokinetics; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010649:Phenylalanine / Q000493:pharmacokinetics; D011247:Pregnancy; D012756:Sheep
D000418:Albumins; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D010100:Oxygen