Elevated IGF-II mRNA and phosphorylation of 4E-BP1 and p70 in muscle showing clenbuterol-induced anabolism

Sneddon, A. A., M. I. Delday, J. Steven, and C. A. Maltin. Elevated IGF-II mRNA and phosphorylation of 4EBP1 and p70S6k in muscle showing clenbuterol-induced anabolism. Am J Physiol Endocrinol Metab 281: E676–E682, 2001.—Muscle wasting affects large numbers of people, but few therapeutic approaches exist to treat and/or reverse this condition. The b2-adrenoceptor agonist clenbuterol produces a muscle-specific protein anabolism in both normal and catabolic muscle and has been used to limit muscle wasting in humans. Because clenbuterol appears to interact with or mimic innervation, its effect on the expression of the neurotrophic agents insulin-like growth factor (IGF)-II and H19 and their putative pathways was examined in normal rat plantaris muscle. The results showed that the well-documented early effects of clenbuterol on protein metabolism were preceded by elevated levels of IGF-II and H19 transcripts together with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) and p70S6k. By 3 days, transcript levels for IGF-II and H19 and 4E-BP1 and p70S6k phosphorylation had returned to control values. These novel findings indicate that clenbuterol-induced muscle anabolism is potentially mediated, at least in part, by an IGF-II-induced activation of 4E-BP1 and p70S6k.