Abstract
In this study in sheep with differing nutritional status, the authors present a model to investigate local as well as systemic effects of recombinant IGF-1 on hind limb muscle metabolism. Recombinant human IGF-1 (12.3;jbg-kg-h) was infused for 4 hours directly into the left femoral artery. The rates of protein synthesis, degradation, and gain of protein in the treated (infused) and contralateral limbs of well-fed, feeding-restricted, and starved sheep were calculated by the kinetics of L-12,6-_Hlphenylalanine infused into the jugular vein (8.5 kBq-min for 8 hours). Reducing feed intake decreased net protein gain of hind limb muscles, reduced hind limb glucose uptake, and lowered arterial concentration of IGF-1, insulin, glucose, phenylalanine, tyrosine, and isoleucine. The effect of nutrition on IGF binding proteins (IGFBP) was generally small; IGFBP-2 was more abundant in fasted animals. Infusion of IGF-1 into the left femoral artery increased plasma IGF-1 levels 2- to 4-fold in the left femoral vein, and by 1.5- to 3-fold in the artery and right femoral vein. In the IGF-1 infused left limb, IGF-1 reduced protein degradation, increased protein gain, and increased glucose uptake, without alterations in blood flow or oxygen uptake, regardless of feed intake. Systemically, IGF-1 reduced plasma concentrations of insulin, phenylalanine, tyrosine, isoleucine, and leucine in all nutrition groups. Plasma IGFBP-3 levels were increased by 4 hours of IGF-1 treatment in fasted but not in fed lambs. In fed but not fasted lambs, IGF-I increased blood glucose concentration. Effects of IGF-1 on protein metabolism in the right hind limb were affected by nutrition to a greater extent in fasted than in fed lambs.
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