BACKGROUND Skeletal muscle atrophy is characterized by muscle wasting with partial or complete functional loss. Skeletal muscle atrophy severely affects the quality of life and currently, there is no available therapy except for spinal muscular atrophy. OBJECTIVE Drug repositioning is a promising strategy that reduces cost and time due to prior availability of safety and toxicity details. Here we investigated myogenic and anti-atrophy effects of glucagon-like peptide-1 (GLP-1) analog liraglutide. METHODS We used several in vitro atrophy models in C2C12 cells and in vivo models in Sprague Dawley rats to study Liraglutide's efficacy. Western blotting was used to assess cAMP-dependent signaling pathways specifically activated by liraglutide. Therapeutic efficacy of liraglutide was investigated by histological analysis of transverse muscle sections followed by morphometry. Myogenic capacity was investigated by immunoblotting for myogenic factors. RESULTS Liraglutide induced myogenesis in C2C12 myoblasts through GLP-1 receptor via a cAMP-dependent complex network of signaling events involving protein kinase A, phosphoinositide 3-kinase/protein kinase B, p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. Liraglutide imparted protection against freeze injury, denervation, and dexamethasone -induced skeletal muscle atrophy and improved muscular function in all these models. In a therapeutic model, liraglutide restored myofibrillar architecture in ovariectomy-induced atrophy. Anti-atrophy actions of liraglutide involved suppression of atrogene expression and enhancement in expression of myogenic factors. CONCLUSION Liraglutide imparted protection and restored myofibrillar architecture in diverse models of muscle atrophy. Given its potent anti-atrophy, and recently reported osteoanabolic effects, we propose liraglutide's clinical evaluation in skeletal muscle atrophy and musculoskeletal disorders associated with diverse pathologies.

中文翻译：

---

长效GLP-1类似物利拉鲁肽可改善啮齿动物的骨骼肌萎缩。

背景技术骨骼肌萎缩的特征在于具有部分或全部功能丧失的肌肉消瘦。骨骼肌萎缩严重影响生活质量，目前，除了脊柱肌肉萎缩之外，没有其他可用的疗法。目的药物重新定位是一种有前途的策略，由于事先可获得安全性和毒性详细信息，因此可以降低成本和时间。在这里，我们研究了胰高血糖素样肽1（GLP-1）类似物利拉鲁肽的生肌和抗萎缩作用。方法我们使用了几种C2C12细胞体外萎缩模型和Sprague Dawley大鼠体内模型来研究利拉鲁肽的疗效。Western印迹用于评估被liraglutide特异性激活的cAMP依赖性信号通路。通过对横肌切片进行组织学分析，然后进行形态测定，研究了利拉鲁肽的治疗效果。通过针对肌原性因子的免疫印迹研究了肌原性能力。结果利拉鲁肽通过cLP依赖的信号蛋白事件复杂网络组成的复杂网络，通过GLP-1受体诱导C2C12成肌细胞发生肌病，​​涉及蛋白激酶A，磷酸肌醇3激酶/蛋白激酶B，p38丝裂原活化蛋白激酶和细胞外信号调节激酶。利拉鲁肽在所有这些模型中均具有抗冻伤，去神经支配和地塞米松诱导的骨骼肌萎缩的保护作用，并改善了肌肉的功能。在治疗模型中，利拉鲁肽在卵巢切除术引起的萎缩中恢复了肌原纤维的结构。利拉鲁肽的抗萎缩作用涉及抑制星形基因的表达和增强肌原性因子的表达。结论利拉鲁肽可在多种肌肉萎缩模型中提供保护并恢复肌原纤维结构。鉴于其有效的抗萎缩作用，以及最近报道的骨合成代谢作用，我们建议利拉鲁肽在骨骼肌萎缩症和与各种病理相关的肌肉骨骼疾病中的临床评价。