[beta]2-Adrenergic receptor ([beta]2-AR) agonist formoterol suppresses differentiation of L6 myogenic cells by blocking PI3K-AKT pathway

[beta]2-Adrenergic receptor ([beta]2-AR) is implicated in muscle metabolic activities such as glycogen metabolism, glucose uptake, lipolysis and muscle growth. However, the functional role of [beta]2-AR in the differentiation of skeletal muscle is largely unknown. Here, we examined the functional role of [beta]2-AR in L6 myoblast differentiation using the long-term-acting [beta]2-AR-specific agonist formoterol. We observed that formoterol treatment strongly suppressed L6 myoblast differentiation and the expression of myosin heavy chain (MHC) in a dose- and time-dependent manner. Showing that both long-acting agonist (formoterol) and short-acting agonist (terbutaline) inhibited the induction of MHC protein, whereas [beta]2-AR antagonist (ICI-118,551) upregulated MHC expression, we clearly demonstrated that [beta]2-AR is involved in L6 myoblast differentiation. Furthermore, our pharmacological inhibition study revealed that the PI3K-AKT pathway is the main signaling pathway for myotube formation. Formoterol inhibited the activation of PI3K-AKT signaling, but not that of ERK signaling. Moreover, formoterol selectively inhibited AKT activation by IGF-I, but not by insulin. Collectively, our findings reveal a previously undocumented role of [beta]2-AR activation in modulating the differentiation of L6 myoblasts.