FoxO1 is crucial for sustaining cardiomyocyte metabolism and cell survival
Bibliographic record
Abstract
Diabetic cardiomyopathy is a term used to describe cardiac muscle damage-induced heart failure. Multiple structural and biochemical reasons have been suggested to induce this disorder. The most prominent feature of the diabetic myocardium is attenuated insulin signalling that reduces survival kinases (Akt), potentially switching on protein targets like FoxOs, initiators of cell death. FoxO1, a prominent member of the forkhead box family and subfamily O of transcription factors and produced from the FKHR gene, is involved in regulating metabolism, cell proliferation, oxidative stress response, immune homeostasis, pluripotency in embryonic stem cells, and cell death. In this review we describe distinctive functions of FoxOs, specifically FoxO1 under conditions of nutrient excess, insulin resistance and diabetes, and its manipulation to restore metabolic equilibrium to limit cardiac damage due to cell death. Because FoxO1 helps cardiac tissue to combat a variety of stress stimuli, it could be a major determinant in regulating diabetic cardiomyopathy. In this regard, we highlight studies from our group and others who illustrate how cardiac tissue-specific FoxO1 deletion protects the heart against cardiomyopathy and how its down-regulation in endothelial tissue could prevent against atherosclerotic plaques. In addition, we also describe studies that show FoxO1's beneficial qualities by highlighting their role in inducing anti-oxidant, autophagic, and anti-apoptotic genes under stress conditions of ischaemia-reperfusion and myocardial infarction. Thus, the aforementioned FoxO1 traits could be useful in curbing cardiac tissue-specific impairment of function following diabetes.
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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".