ABSTRACT β2-Adrenergic receptor (β2-AR) is implicated in muscle metabolic activities such as glycogen metabolism, glucose uptake, lipolysis and muscle growth. However, the functional role of β2-AR in the differentiation of skeletal muscle is largely unknown. Here, we examined the functional role of β2-AR in L6 myoblast differentiation using the long-term-acting β2-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 β2-AR antagonist (ICI-118,551) upregulated MHC expression, we clearly demonstrated that β2-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 β2-AR activation in modulating the differentiation of L6 myoblasts.

中文翻译：

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β2-肾上腺素能受体 (β2-AR) 激动剂福莫特罗通过阻断 PI3K-AKT 通路抑制 L6 肌细胞分化

摘要 β2-肾上腺素能受体 (β2-AR) 与肌肉代谢活动有关，如糖原代谢、葡萄糖摄取、脂肪分解和肌肉生长。然而，β2-AR 在骨骼肌分化中的功能作用在很大程度上是未知的。在这里，我们使用长效 β2-AR 特异性激动剂福莫特罗检查了 β2-AR 在 L6 成肌细胞分化中的功能作用。我们观察到福莫特罗治疗以剂量和时间依赖性方式强烈抑制 L6 成肌细胞分化和肌球蛋白重链 (MHC) 的表达。显示长效激动剂（福莫特罗）和短效激动剂（特布他林）均抑制 MHC 蛋白的诱导，而 β2-AR 拮抗剂（ICI-118,551）上调 MHC 表达，我们清楚地证明 β2-AR 参与 L6成肌细胞分化。此外，我们的药理抑制研究表明，PI3K-AKT 通路是肌管形成的主要信号通路。福莫特罗抑制 PI3K-AKT 信号的激活，但不抑制 ERK 信号的激活。此外，福莫特罗通过 IGF-I 选择性抑制 AKT 激活，但不能通过胰岛素抑制。总的来说，我们的研究结果揭示了 β2-AR 激活在调节 L6 成肌细胞分化中的先前未记录的作用。