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AJP - Endocrinology and Metabolism, Vol 270, Issue 1 E60-E66, Copyright © 1996 by American Physiological Society
ARTICLES |
R. Jacob, X. Hu, D. Niederstock, S. Hasan, P. H. McNulty, R. S. Sherwin and L. H. Young
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Infusion of insulin-like growth factor I (IGF-I) lowers plasma amino acid and insulin concentrations, which may limit the capacity of IGF-I to promote muscle protein synthesis in vivo. We measured heart and skeletal muscle incorporation of continuously infused L-[ring-2,6-3H]phenylalanine in awake postabsorptive rats receiving 4-h intravenous infusions of saline (n = 11), IGF-I (1 microgram.kg-1.min-1) with (n = 10) or without (n = 11) amino acid replacement, or IGF-I with insulin replacement (n = 8). There were no significant increases in muscle protein synthesis during the infusion of IGF-I alone, which was associated with decreases in both plasma insulin (52 +/- 5%, P < 0.001) and amino acids (25 +/- 5%, P < 0.05). When IGF-I was given together with amino acids, protein synthesis was significantly increased in gastrocnemius (4.7 +/- 0.4 vs. 2.5 +/- 0.3%/day, P < 0.001), oblique (4.5 +/- 0.4 vs. 2.8 +/- 0.4%/day, P < 0.05), and soleus (8.8 +/- 0.7 vs. 6.4 +/- 0.3%/day, P < 0.01) and tended to be higher than saline control values in heart (10.9 +/- 0.9 vs. 8.8 +/- 0.7%/day, P = 0.08). Amino acid replacement prevented plasma concentrations from falling and also blunted the decline in plasma insulin (22 +/- 5%, P < 0.01 vs. IGF-I alone). When IGF-I and insulin replacement were given, protein synthesis was increased in heart (13.0 +/- 0.6%/day), gastrocnemius (4.7 +/- 0.4%/day), and oblique (4.5 +/- 0.4%/day) (P < 0.001 for each, compared with saline). We conclude that the action of IGF-I to acutely stimulate muscle protein synthesis in the awake rat is limited by the fall in circulating insulin and/or amino acid concentrations that accompanies IGF-I infusion in vivo and is prevented by co-infusion of insulin or amino acids.
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