RESUMEN
The involvement of circulating insulin-like growth factor-I (IGF-I) in the skeletal muscle response to resistance exercise is currently unclear. To address this, we utilized the liver IGF-I-deficient (LID) mouse model, in which the igf1 gene has been disrupted in the hepatocytes, resulting in ~80% reduction in serum IGF-I. Twelve- to 13-month-old male LID and control (L/L) mice were subjected to 16 weeks of resistance training. Resistance exercise resulted in equal strength gains in both L/L and LID mice. Basal IGF-I mRNA levels were greater in LID muscles than in L/L, and exercise increased IGF-I mRNA in quadriceps, gastrocnemius, and plantaris muscles. LID mice had elevated tyrosine phosphorylation of IGF-IR and Stat5b, the latter possibly reflective of increased serum GH. Tyrosine phosphorylation of IGF-IR was increased, while phospho-Stat5b was reduced after resistance training of both wild-type and LID mice. These data suggest that: 1) performance and recovery in response to resistance training is normal even when there is severe deficiency of circulating IGF-I; and 2) upregulation of local IGF-I may be involved in the compensatory growth of muscle that occurs in response to resistance training. Decreased levels of p-Stat5b in exercised mice suggests that the upregulation of local IGF-I gene expression in response to exercise may be GH-independent.
Asunto(s)
Factor I del Crecimiento Similar a la Insulina/deficiencia , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Condicionamiento Físico Animal/fisiología , Animales , Peso Corporal , Regulación de la Expresión Génica , Hipertrofia , Factor I del Crecimiento Similar a la Insulina/genética , Masculino , Ratones , Tamaño de los Órganos , Músculo Cuádriceps/metabolismo , Músculo Cuádriceps/patología , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
This study investigated the effect of age on recovery of skeletal muscle from an ischemia-reperfusion (I/R)-induced injury. Young (6 mo old) and old (24-27 mo old) Sprague-Dawley rats underwent a 2-h bout of hindlimb ischemia induced by a pneumatic tourniquet (TK). The TK was released to allow reperfusion of the affected limb, and animals were divided into 7- and 14-day recovery groups. Maximum plantar flexor force production was assessed in both 7- and 14-day recovery groups of both ages, followed by histological evaluation. Subsequent analysis of IGF-I gene expression and intracellular signaling in 7-day recovery muscles was performed by RT-PCR and Western blotting, respectively. Old rats had significantly greater deficits in force production and exhibited more evidence of histological pathology than young at both 7 and 14 days postinjury. In addition, old rats demonstrated an attenuated upregulation of IGF-I mRNA and induction of proanabolic signaling compared with young in response to injury. We conclude that aged skeletal muscle exhibits more damage and/or defective regeneration following I/R and identify an age-associated decrease in local IGF-I responsiveness as a potential mechanism for this phenomenon.