Elevated IGF-II mRNA and phosphorylation of 4E-BP1 and p70(S6k) in muscle showing clenbuterol-induced anabolism

Muscle wasting affects large numbers of people, but few therapeutic approac hes exist to treat and/or reverse this condition. The beta (2)-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 neuro trophic agents insulin-like growt h factor, (IGF)-II and H19 and their putative pathways was examined in norm al rat plantaris muscle. The results showed, that the well-documented early effects of clenbuterol on protein metabolism were preceded by elevated lev els of IGF-II and H19 transcripts together with increased phosphorylation o f eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) and p70(S 6k). By 3 days, transcript levels for IGF-II and H19 and 4E-BP1 and p70(S6k ) phosphorylation had returned to control values. These novel findings indi cate that clenbuterol-induced muscle anabolism is potentially mediated, at least in part, by an IGF-II-induced activation of 4E-BP1 and p70(S6k).