Insulin-like growth factor 1 inhibits degradation and improves retention of protein in hindlimb muscle of lambs.

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.