Serine modulates insulin resistance during short-term bed rest

Background Insulin resistance (IR) manifesting as a result of muscle unloading is often accompanied by an altered amino acid (AA) profile. The aim of this study was to assess the potential impact of AAs on IR during inactivity. Methods Plasmatic AA, glucose, and insulin were retrospectively analyzed from three different bed rest studies (BR1, BR2, BR3) involving 26 young healthy males. Since AAs were analyzed on different days, we imputed all missing values with multivariate imputation by chained equations, which allowed us to evaluate trends of plasmatic AAs in relation to IR (HOMA IR) during 9 d of inactivity. A generalized linear mixed model (GLMM) was fitted to examine the effect of selected plasmatic AAs (predictors) on HOMA IR (outcome). Results of GLMM were further validated with data from BR1 and BR2 (19 subjects), in which AAs were analyzed on days 1, 5, and 9. Results Serine exhibited a sig. negative fixed effect on HOMA IR [−0,015] ( P = 0.006), while HOMA-IR had no sig. effect on serine ( P = 0.507), suggesting a unidirectional relationship. Furthermore, data from BR1 and BR2 confirmed the inverse effect: serine levels sig. increased during the initial days (+13%), followed by a sig. drop from fifth to the ninth d (−6.5%). When serine was available, HOMA IR was not sig. affected. When serine availability dropped, HOMA IR continued to rise, reaching a sig. difference from baseline values to ninth d of BR (+27%). Conclusion Our findings indicate that serine can have an inverse impact on IR and not vice versa. Upholding serine levels during short-term BR could have a protective role against IR.