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
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".