Chronic metformin treatment induces beneficial adaptations in dystrophic skeletal muscle
Bibliographic record
Abstract
DMD is the most severe inherited neuromuscular disorder for which there is no effective treatment. Our pre‐clinical studies in mdx mice demonstrated that pharmacological activation of PPARβ/γ or AMPK elicits a fiber type shift towards the slower, more oxidative (SO) phenotype together with utrophin A upregulation thereby attenuating the dystrophic pathology (HMG, 18:2640, 2009; HMG, 20:3478, 2011; AJP Cell 302:C110, 2012). The challenge now is to identify agonists of these pathways that have more immediate clinical relevance. The purpose of this study was to investigate whether AMPK stimulation via metformin (MET), a front‐line drug in the treatment of type 2 diabetes, induces beneficial muscle remodeling. In C2C12 cells, MET augmented expression of PGC‐1α, a master regulator of the SO myogenic program, as well as utrophin A levels. MET treatment of mdx mice for 6 weeks resulted in an increase in PGC‐1α in fast skeletal muscle with a concomitant reduction of the transcriptional corepressor RIP140. Expression of utrophin A was also augmented after MET administration in vivo. The data clearly suggest that MET‐induced reciprocal changes in PGC‐1α and RIP140 expression are linked to elevations in utrophin A content. As these adaptations are expected to be highly beneficial to dystrophic fibers, we propose that MET represents a novel and promising therapeutic avenue for DMD. Supported by MDA, CIHR, and Jesse's Journey.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".