Research On The Mechanism Of Skeletal Muscle Hypertrophy Induced By IGF-I And Exercise

Objective:To study the effect and regulating mechanism of PI3K/Akt/mTOR signaling pathway on protein synthesis in skeletal muscle which is stimulated by IGF-I.Methods:Adult male Sprague-Dawley rats were randomly divided to eight groups:sedentary group(S), sedentary and IGF-I injection group(SI), sedentary and LY294002 injection group(SL), sedentary and IGF-I plus LY294002 injection group (SIL),exercise group(E), exercise and IGF-I injection group(El), exercise and LY294002 injection group(EL), exercise and IGF-I plus LY294002 injection group (EIL).After all the groups had been adapted for one week, the rats of four exercise groups performed closely monitored formal training in treadmills (gradient of 10%, at the speed of 20m/min and duration of 60min/day)for one week. All the injection groups were injected at the same time immediately after exercise every day. After the 7 days of normal training, the gastrocnemius musle of the injection side were collected at the 6th hour post exercise. Protein content of gastrocnemius muscle was assessed with Bradford. Protein expression of PI3K, Akt, mTOR, p70S6K and phosphorylation of Akt (Ser473),mTOR (Ser2448), p70S6K (Thr389) were measured by Western Blot.Results:(1)One week LY294002 injection inhibit the protein expression of Akt, mTOR, p70S6K and the phosphorylation of AktB (Ser473),mTOR (Ser2448), p70S6K (Thr389);(2)One-week IGF-1 injection increased the wet gastrocnemius muscle weight significantly, and promoted the protein expression of PI3K, Akt, mTOR, p70S6K and phosphorylation of AktB (Ser473), mTOR (Ser2448), p70S6K (Thr389) significantly. (3))One-week endurance exercise increased the protein expression of PI3K, Akt, mTOR, p70S6K and the phosphorylation of AktB (Ser473),mTOR (Ser2448), p70S6K(Thr389)at the 6th hour of recovery period; (4) exercise plus IGF-I injection has higher level of the protein expression of PI3K/Akt/mTOR signaling pathway than exercise or IGF-I respectively. Conclusion:(1)IGF-I is a potent activator of muscle growth and appears to mediate this effect through the activation of the PI3K/Akt/mTOR signaling pathway.(2)LY294002 can significantly suppress the activation of PI3K/Akt/mTOR signaling pathway.(3) Both exercise an IGF-I injection can weaken the inhibition effect of LY294002.(4)Exercise and IGF-I injection have an accumulative effect on the activation of PI3K/Akt/mTOR signaling pathway.