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Appl Physiol Nutr Metab. 2007 Dec;32(6):1115-23.

Rat hindlimb unloading down-regulates insulin like growth factor-1 signaling and AMP-activated protein kinase, and leads to severe atrophy of the soleus muscle.

Author information

1
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.

Abstract

Inactivity is known to induce muscle atrophy, which is associated with insulin and insulin-like growth factor-1 (IGF-1) resistance, but the associated mechanisms remain poorly defined. The hindlimb unloading model has been used to reduce muscle activity. The objective of this study was to show the effect of hindlimb unloading on IGF-1 signaling and AMP-activated protein kinase (AMPK) activity in rat soleus and extensor digitorum longus (EDL) muscles. Twelve 7-week-old male Sprague-Dawley rats were assigned to 2 treatments: (i) rats without hindlimb unloading (Con) and (ii) rats with hindlimb unloading (Unload). After 2 weeks of treatment, the soleus and EDL muscles were dissected and used for biochemical analyses. Hindlimb unloading induced severe muscle atrophy in soleus muscle (0.122+/-0.007 g for Con vs. 0.031+/-0.004 g for Unload, p<0.01), but only slight atrophy in EDL muscle. The phosphorylation of AMPK (p<0.05) and its downstream substrate, acetyl-CoA carboxylase (ACC) (p<0.01) were reduced in soleus muscle due to unloading. The concentration of insulin receptor substrate-1 (IRS-1) and phosphorylation of IRS-1 at Ser636-639 and Ser789 were also reduced. Downstream IGF-1 signaling was downregulated in Unload rats. A reduction in IGF-1 concentration in unloaded soleus muscle was also observed. A slight reduction in AMPK activity and IGF-1 signaling were observed in EDL muscle. Since AMPK controls the sensitivity of IGF-1 signaling through phosphorylation at Ser789, the reduction in AMPK activity is expected to reduce the response of downstream IGF-1 signaling to IGF-1; this, in combination with reduced IGF-1 concentration, might be responsible for the severe muscle atrophy observed in unloaded soleus muscle.

PMID:
18059585
DOI:
10.1139/H07-102
[Indexed for MEDLINE]

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