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A functional IGF‐I receptor is not necessary for in vivo skeletal muscle hypertrophy
Author(s) -
Spangenburg Espen E,
LeRoith Derek,
Bodine Sue
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1303-a
Subject(s) - medicine , endocrinology , muscle hypertrophy , plantaris muscle , skeletal muscle , phosphorylation , protein kinase b , biology , chemistry , soleus muscle , biochemistry
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).