Background. Type 2 diabetes mellitus increases the risk of sarcopenia, which is characterized by decreased muscle mass, strength, and function. However, there are no effective drugs to treat diabetic sarcopenia, and its underlying mechanism remains unknown. Here, we aimed to determine whether the GLP-1 receptor agonist (GLP-1RA) dulaglutide (Dul) affects the progression of diabetic sarcopenia. Methods. db/db mice were injected intraperitoneally with 0.6 mg/kg dulaglutide for 10 weeks. Mouse muscle tissues were then pathologically evaluated and stained with F4/80 or MPO to detect macrophages and neutrophils, respectively. In addition, inflammatory factors and FNDC5 in the muscle tissues were detected using qRT-PCR. Moreover, C2C12 cells were induced to enable their differentiation into skeletal muscle cells, and muscle factor levels were then detected. Furthermore, changes in muscle factor levels were detected at various glucose concentrations (11 mM, 22 mM, and 44 mM). Results. In vivo, dulaglutide alleviated muscle tissue injury; reduced levels of the inflammatory factors, IL-1β, IL-6, CCL2, and CXCL1; and reversed the level of FNDC5 in the muscle tissues of db/db mice. In vitro, a C2C12 cell differentiation model was established through the observation of cell morphology and determination of myokine levels. Upon stimulation with high glucose, the differentiation of C2C12 cells was inhibited. Dulaglutide improved this inhibitory state by upregulating the levels of both FNDC5 mRNA and protein. Conclusions. Treatment with the GLP-1RA dulaglutide protects db/db mice against skeletal muscle injury by inhibiting inflammation and regulating the differentiation of myoblasts. High glucose inhibited the differentiation of C2C12 cells and decreased the mRNA and protein levels of myokines. Dulaglutide could reverse the differentiation state induced in C2C12 cells by high glucose.

中文翻译：

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度拉鲁肽通过抑制炎症和调节成肌细胞分化来保护小鼠免受糖尿病肌少症介导的肌肉损伤

背景。2 型糖尿病会增加肌肉减少症的风险，其特点是肌肉质量、力量和功能下降。然而，目前尚无治疗糖尿病肌少症的有效药物，其潜在机制仍不清楚。在这里，我们的目的是确定 GLP-1 受体激动剂 (GLP-1RA) 度拉鲁肽 (Dul) 是否会影响糖尿病肌少症的进展。方法。db/db小鼠腹腔注射0.6mg/kg度拉鲁肽，持续10周。然后对小鼠肌肉组织进行病理学评估，并用 F4/80 或 MPO 染色，分别检测巨噬细胞和中性粒细胞。此外，使用qRT-PCR检测肌肉组织中的炎症因子和FNDC5。此外，诱导C2C12细胞分化为骨骼肌细胞，然后检测肌肉因子水平。此外，在不同的葡萄糖浓度（11 mM、22 mM 和 44 mM）下检测到肌肉因子水平的变化。结果。在体内，度拉鲁肽减轻了肌肉组织损伤；炎症因子 IL-1 β、IL-6、CCL2 和 CXCL1 水平降低；并逆转了 db/db 小鼠肌肉组织中的 FNDC5 水平。在体外，通过细胞形态观察和肌因子水平测定，建立C2C12细胞分化模型。高葡萄糖刺激后，C2C12细胞的分化受到抑制。度拉鲁肽通过上调 FNDC5 mRNA 和蛋白质的水平来改善这种抑制状态。结论。GLP-1RA 度拉糖肽治疗可通过抑制炎症和调节成肌细胞分化来保护 db/db 小鼠免受骨骼肌损伤。高糖抑制C2C12细胞的分化并降低肌因子的mRNA和蛋白水平。度拉鲁肽可以逆转高糖诱导的C2C12细胞的分化状态。