Sarcopenia is the gradual decrease of skeletal muscle mass during aging. Due to absence of clear clinical indicator, it is required to develop useful biomarkers that can be quantified in a feasible, accessible manner and that can accompany diagnosis and therapy of pathological muscle atrophy in general clinical practice and clinical trials. Recently, the presence of low muscle mass and low muscle function have been proposed as parameters for the diagnosis of sarcopenia. In addition, inclusion of serum markers was also suggested so as to constitute an optimal biomarker panel. However, there is a lack of serum biomarkers that can reflect the diagnostic imaging of muscle mass. Skeletal muscles have recently been established as an endocrine organ. Irisin is one of myokines derived from skeletal muscle and is known to be induced upon vigorous exercise and to facilitate thermogenesis of adipocyte. Furthermore, it is predominantly expressed in skeletal muscle compared to other tissues.The aim of this study is to determine whether atrophic and hypertrophic myotube remodeling alter FNDC5/irisin expression and/or secretion levels in vitro. To investigate myotube diameter-dependent expression and secretion of irisin, we applied dexamethasone (DEX) and insulin-like growth factor 1 (IGF-1) to induce myotube atrophy and/or hypertrophy, respectively. FNDC5/Irisin protein expression significantly increased during myogenic differentiation, which was paralleled by increased irisin secretion. Additionally, the release of irisin was time-dependent detected from conditioned medium (CM) of C2C12 myotubes. C2C12 myotubes secreted about few ng/ml irisin during 24 hours from differentiated 1*105 cells of C2C12 myoblast seeded on 6-well plate. DEX and IGF-1 significantly induced myotubes atrophy and hypertrophy, which were paralleled by decreased and increased irisin secretion levels, respectively. IGF-1 treatment released irisin secretion in a dose dependent manner. Akt phosphorylation was detected by IGF-1 which was blocked by treatment of PI3K inhibitor (LY294002), Erk1/2 inhibitor (u0126) or mTOR inhibitor (rapamycin) indicating that both Akt and Erk1/2 signaling pathways are crucial for secretion of irisin. Furthermore, Akt activators (IGF1 and insulin) which counteract atrophic remodeling of myotube, as well as AMPK activators (AICAR and metformin) attenuated dexamethasone-induced decrease of irisin secretion.Taken together, level of irisin in conditioned medium mirrors myotube diameters in culture condition. Therefore, it may be considered as a potential biomarker for muscular atrophy.