Dexamethasone 유도 골격근 위축 모델에서 C-peptide의 근감소 예방 효과

Abstract

Skeletal muscle accounts for about 40% of total body weight and is involved in physical activity and energy metabolism in human. Skeletal muscle weight is regulated by the signaling balance of muscle synthesis or degradation. When muscle degradation exceeds synthesis, it results in muscle atrophy which leads to a decrease in muscle weight, muscle strength, muscle fiber, and fatigue resistance. Dexamethasone (DEX) is a glucocorticoid medication known to cause muscle atrophy. C-peptide, which is secreted by pancreatic beta cells, has been reported to have various biological activities. However, its effect on muscle atrophy has not been reported yet. Thus, in this study, we investigated the effect of C-peptide on a DEX-induced atrophy model. For in vitro study, C2C12 myotubes were incubated with or without DEX and subsequently treated with various concentrations (0, 0.01, 0.1, 1, 10, 100 nM) of C-peptide to evaluate its effect on cell differentiation and regulation muscle atrophic factors. C-peptide inhibited the expression of muscle atrophic factors at low concentrations. Conversely, at high concentrations, the expression of muscle atrophic factors was enhanced in C2C12 cell. For in vivo study, C57BL/6J mice were divided into three groups. The control (CON) and DEX groups were injected intraperitoneally with saline or DEX, respectively, for 8 days, followed by saline injection for 12 days. DEX + C-peptide group was injected with DEX and C-peptide simultaneously for 8 days, followed by C-peptide injection 12 days. As a result, C-peptide significantly augmented body weight and muscle weight in the DEX + CP group compared to the DEX group. Moreover, C-peptide inhibited the expression of muscle atrophy factors, such as Atrogin-1, in the muscles. In conclusion, this study suggests that C-peptide has potential to improve muscle atrophy by ameliorating protein degradation in muscles.