Hypertrophy w/o IGF receptor signaling

Posted 16 February 2008 - 10:22 PM (#1) Heavy_Lifter85

The Balls

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J Physiol 586.1 (2008) pp 283–291

A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy

Increasing the mechanical load on skeletalmuscle results in increased expression of insulin-like growth factor I (IGF-I), which is thought to be a critical step in the induction of muscle hypertrophy. To determine the role of the IGF-I receptor in load-induced skeletal muscle hypertrophy, we utilized a transgenic mouse model (MKR) that expresses a dominant negative IGF-I receptor specifically in skeletalmuscle. Skeletalmuscle hypertrophy was induced in the plantarismuscle using the functional overload (FO) model, amodel which has previously been shown to induce significant elevations of IGF-I expression in skeletal muscle. Adult male wild-type (WT) andMKRmice were subjected to 0, 7 or 35 days of FO. In control or unchallenged animals, the plantaris mass was 11% greater in WT compared to the MKR mice (P <0.05). After 7 days of FO, plantaris mass increased significantly by 26% and 62% in WT and MKR mice, respectively (P <0.05). After 35 days of FO,WTand MKR mice demonstrated significant increases of 100% and 122%, respectively, in plantaris mass (P <0.05). Further, at no time point was the degree of hypertrophy significantly different between the WT and MKR mice. Previous research suggests that IGF-I induces muscle growth through activation of the Akt–mTOR signalling pathway; therefore, we measured the phosphorylation status of Akt and p70s6k in theWTand MKR mice after 7 days of FO. Significant increases of∼100% and∼200% in Akt (Ser-473) and p70s6k (Thr-389) phosphorylation were measured in overloaded plantaris from both WT and MKR mice, respectively. Moreover, no differences were detected between the WT and MKR mice. These data suggest that increased mechanical load can induce muscle hypertrophy and activate the Akt and p70s6k independent of a functioning IGF-I receptor.

Posted 17 February 2008 - 06:32 AM (#2) fitnecise

tweedle dum

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Yep, this was actually published a couple months ago in the same journal also. This studied endogenous IGF-1 in response to loading, there is still research supporting exogenous for hypertrophy (plus this is rats)

From that paper:

Quote

The anabolic effects of IGF-1 have been demonstrated in both muscle cell lines and in vivo animal models (Adams & McCue, 1998; Chakravarthy et al., 2000; Rommel Spangenburg et al. Skeletal muscle hypertrophy 4 et al., 2001; Vyas et al., 2002). For example, the addition of exogenous IGF-I to cultured myotubes results in an enlargement of myotube diameters and a higher protein content (Rommel et al., 2001; Vyas et al., 2002), while the delivery of exogenous IGF-I either through osmotic pumps or genetic over-expression results in enhanced muscular mass in rodents (Adams & McCue, 1998; Musaro et al., 2001). However, IGF-I alone does not seem to prevent muscle atrophy (Criswell et al., 1998). Thus, it is clear that the addition of exogenous IGF-I to muscle can effectively induce muscle growth. However, at this time no data have convincingly determined if the endogenous IGF-I system is the key factor necessary for initiation of the growth response that occurs in muscle following the application of chronic mechanical load.

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