A functional IGF‐I receptor is not necessary for in vivo skeletal muscle hypertrophy

Abstract

To determine the role of the IGF-I receptor in skeletal muscle hypertrophy, we utilized a transgenic mouse model that expresses a dominant negative IGF-I receptor specifically in skeletal muscle (MKR). Muscle hypertrophy was induced by using the functional overload model (FO) of the plantaris muscle. This model results in significant elevations of IGF-I expression in skeletal muscle. Adult male wild type (WT) and MKR mice were subjected to non-FO, 7 or 35 days of FO. In the non-FO animals, plantaris mass was 11% (p<0.05) greater in WT compared to MKR mice. After 7 days of FO, plantaris mass significantly increased by 37 and 48 % in WT and MKR mice, respectively. After 35 days of FO, the WT and MKR mice demonstrated significant increases in plantaris mass of 98% and 122%, respectively. However, at no time point after the FO were significant differences detected in plantaris mass between the WT and MKR mice. Previous research suggests that IGF-I-induces muscle growth through activation of the Akt-mTOR signaling pathway. Therefore, we measured the phosphorylation status of Akt and p70s6k in the WT and MKR mice after 7 days of FO. There were significant increases in Akt (Ser-473) and p70s6k (Thr-389) phosphorylation in both the WT and MKR mice when compared to the non-FO WT and MKR mice. However, no significant differences were detected in phosphorylation between the WT and MKR mice at 7 days if FO. These data suggest that increased mechanical load can induce muscle growth and activate Akt and p70s6k independent of a functioning IGF-I receptor. Supported by NIH AR051396 (EES) and NIH NIDDK (DLR).