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.
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