This study tested the hypothesis that an isometric
resistance training paradigm targeting the medial gastrocnemius of adult rodents is effective in preventing
muscle atrophy during the early stages of hindlimb unloading by maintaining normal activation of the
insulin receptor substrate-1 (IRS-1)/
phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. This pathway has been shown to simultaneously create an anabolic response while inhibiting processes upregulating catabolic processes involving expression of key
enzymes in the ubiquitination of
proteins for degradation. The findings show that during the 5 days of unloading 1) absolute medial gastrocnemius muscle
weight reduction occurred by approximately 20%, but muscle weight corrected to
body weight was not different from normal weight-bearing controls (P < 0.05); 2) normalized myofibril fraction concentration and content were decreased; and 3) a robust isometric training program, known to induce a
hypertrophy response, failed to maintain the myofibril
protein content. This response occurred despite fully blunting the increases in the
mRNA for of atrogin-1, MURF-1, and
myostatin, e.g., sensitive gene markers of an activated catabolic state. Analyses of the IRS-1/PI3K/Akt markers indicated that abundance of IRS-1 and phosphorylation state of Akt and p70S6
kinase were decreased relative to normal control rats, and the
resistance training failed to maintain these signaling markers at normal regulatory level. Our findings suggest that to fully prevent
muscle atrophy responses affecting the myofibril system during unloading, the volume of mechanical stress must be augmented sufficiently to maintain optimal activity of the IRS-1/PI3K/Akt pathway to provide an effective anabolic stimulus on the muscle.