Dulaglutide Protects Mice against Diabetic Sarcopenia-Mediated Muscle Injury by Inhibiting Inflammation and Regulating the Differentiation of Myoblasts

Abstract

Background. Type 2 diabetes mellitus increases the risk of sarcopenia, which is characterized by decreased muscle mass, strength, and function. However, there are no efective 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) afects 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, infammatory factors and FNDC5 in the muscle tissues were detected using qRT-PCR. Moreover, C2C12 cells were induced to enable their diferentiation 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 infammatory 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 diferentiation model was established through the observation of cell morphology and determination of myokine levels. Upon stimulation with high glucose, the diferentiation 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 infammation and regulating the diferentiation of myoblasts. High glucose inhibited the diferentiation of C2C12 cells and decreased the mRNA and protein levels of myokines. Dulaglutide could reverse the diferentiation state induced in C2C12 cells by high glucose.