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

β(2)-Adrenergic receptor (β(2)-AR) is implicated in muscle metabolic activities such as glycogen metabolism, glucose uptake, lipolysis and muscle growth. However, the functional role of β(2)-AR in the differentiation of skeletal muscle is largely unknown. Here, we examined the functional role of β(2)-AR in L6 myoblast differentiation using the long-term-acting β(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 β(2)-AR antagonist (ICI-118,551) upregulated MHC expression, we clearly demonstrated that β(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 β(2)-AR activation in modulating the differentiation of L6 myoblasts.