Insulin-like growth factor I (
IGF-I) is a potent myogenic factor that plays a critical role in muscle regeneration and muscle
hypertrophy. The purpose of this study was to evaluate the effect of
IGF-I overexpression on the recovery of muscle size and function during reloading/reambulation after a period of cast immobilization in predominantly fast twitch muscles. In addition, we investigated concomitant molecular responses in
IGF-I receptor and
binding proteins (BPs). Recombinant adeno-associated virus vector for
IGF-I (rAAV-IGF-IA) was injected into the anterior compartment of one of the hindlimbs of young (3 wk) C57BL6 female mice. At 20 wk of age, both hindlimbs were cast immobilized in a shortened position for 2 wk to unload the tibialis anterior (TA) and extensor longus digitorum (EDL) muscles. The TA and EDL muscles were removed bilaterally after 2 wk of cast immobilization and after 1 and 3 wk of free cage reambulation. Increases in
IGF-I mRNA and
protein levels with
IGF-I overexpression were associated with significant increases in muscle wet weight, fiber size, and tetanic force, although overexpression did not protect against cast immobilization-induced
muscle atrophy. After 1 wk of reambulation, evidence of enhanced muscle regeneration was noted in
IGF-I-overexpressing muscles with an increased prevalence of central nuclei, embryonic
myosin, and Pax7 positive fibers. We also observed larger relative gains in muscle size (wet weight and fiber area), but not force, during the 3-wk reambulation period in hindlimb muscles overexpressing
IGF-I compared with contralateral control legs. Changes in
IGFBP-5 mRNA expression during cast immobilization and reambulation paralleled those of
IGF-I, whereas
IGFBP-3 expression changed inversely to
IGFBP-5.