Metformin alleviates diastolic dysfunction in mice with experimental diabetic cardiomyopathy
Bibliographic record
Abstract
The first line therapy for managing type 2 diabetes (T2D), metformin, has been shown to be cardioprotective in humans and several preclinical models of cardiovascular disease. However, there has been limited interrogation into metformin's effects on diastolic function, a hallmark characteristic of diabetic cardiomyopathy (DbCM), which is becoming increasingly prevalent in people with pre- and early-stage T2D. Accordingly, we aimed to determine the effects of metformin on the pathogenesis of DbCM and hypothesized that treatment with metformin would alleviate diastolic dysfunction in mice with T2D. To induce experimental T2D and DbCM, male C57BL/6J mice were fed a high-fat diet for 12.5 weeks, in combination with a single, low-dose injection of streptozotocin (75 mg/kg) at week 4.5. The animals' drinking water was randomized to include either vehicle control or metformin (3.0 g/L) during the final 7.5 weeks. As expected, metformin treatment improved glycemia with a trend towards a reduction in adiposity in mice with T2D. Using ultrasound echocardiography, we observed that metformin improved diastolic function in mice with T2D as reflected by an increase and a decrease in the e'/a' and E/e' ratios, respectively. Furthermore, wheat-germ agglutinin staining indicated that treatment with metformin decreased cardiomyocyte hypertrophy in mice with T2D. However, mice with T2D treated with metformin did not exhibit increases in myocardial adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. Thus, our findings suggest that metformin has salutary actions against DbCM and its associated diastolic dysfunction, which may be independent of its ability to increase AMPK activity.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".