Skeletal muscle hypertrophy can be mediated by the induction of insulin-like growth factor-1 (IGF-1), which is a protein growth factor that is sufficient to induce skeletal muscle mass [10, 11]. IGF-1 acts in part by stimulating the phosphatidylinositol-3 kinase (PI3K)/Akt pathway, resulting in the downstream activation of targets that induce protein synthesis [12, 13]. Activation of Akt is sufficient to induce hypertrophy in vivo, as was shown by the production of transgenic mice in which a mutant, constitutively active, form of Akt is conditionally expressed in adult skeletal muscle [14, 15, 16]. Acute activation of Akt in an adult animal, for 2 weeks, was sufficient to induce a doubling in the size of skeletal muscle; this increase occurs via an increase in the average cross-sectional area of individual muscle fibers, caused by an increase in TORC1/p70S6K protein synthesis pathways [14]. Conversely, in settings of skeletal muscle atrophy, Akt activation is downregulated [17].

In addition to stimulating protein synthesis, IGF-1 acts by inhibiting the induction of skeletal muscle atrophy pathways. A distinct set of genes are inversely regulated under IGF-1-induced hypertrophy conditions vs. DEX-induced atrophy [7]; these include the gene MAFbx [18](for Muscle Atrophy F-box; also called Atrogin-1 [19]). A second gene, MuRF1 [18](for Muscle Ring Finger1), is significantly upregulated under atrophy conditions [18]. Both MuRF1 and MAFbx/Atrogin encode E3 ubiquitin ligases [18]. Expression of MuRF1 and MAFbx is