Résumé :
|
In vivo immobilization of muscle at extended length, stimulates IGF-1 expression and induces hypertrophy, however, the mechanisms underlying the high muscle strain induced IGF-1 expression and hypertrophy are unknown. The aim of this study was to investigate the separate effects of sarcomere strain and insulin-like growth factor-1 (IGF-1) on fibre cross-sectional area (CSA), serial sarcomere number and possible synergetic effects of these stimuli. Single muscle fibres were dissected from m. iliofibularis of Xenopus laevis and attached to a force transducer in a culture chamber (20 C). Mature, single muscle fibres of Xenopus laevis were cultured at slack length (sarcomere length 2.3 ?m, "l2.3?m") or at extended length (12% over slack, "high strain") for 10 to 24 days in serum-free medium with or without human recombinant IGF-1. For fibres cultured at l2.3?m without recombinant IGF-1 (1 ?g/ml). tetanic force and CSA remained unchanged. Fibres cultured at high strain without IGF-1 showed a reduction in tetanic force by 1.4±0.2% (mean±SEM) per day (p<0.001), whereas fibre CSA remained constant. In contrast, tetanic force of fibres cultured at l2.3?m with IGF-1 increased by 1.0±0.1% per day (p<0.0001), whereas after 16.6±0.6 days of culture the fibre CSA was increased by 33.4±3.8% (p<0.0001). The fibre CSA of high strain cultured fibres with IGF-1 increased to 28.8±3.7% after 16.6±1.4 days. The IGF-1 induced increase in tetanic force at high stain (0.6±0.2% per day) was lower than at l2.3?m (p<0.001). For all conditions, numbers of sarcomeres in series and myonuclei were unchanged. IGF-1 increased a-skeletal actin mRNA (p<0.03), whereas high strain reduced it. IGF-1 mRNA was doubled by IGF-1 (p<0.0001), but was not affected by high strain. p-Akt concentrations were independent of high strain and/or IGF-1. We conclude that high strain imposed on an isolated muscle fibre causes a reduction in tetanic force and does not stimulate hypertrophy or increase the serial sarcomere number, whereas IGF-1 may stimulate hypertrophic signaling via increasing IGF-1 mRNA and induce hypertrophy by increasing actin mRNA.
|