Metabolic modulation of pyruvate dehydrogenase and glucose oxidation in diabetic cardiomyopathy: pathways, perspectives, and potentials
Bibliographic record
Abstract
Individuals living with obesity and/or type 2 diabetes (T2D) are at a disproportionately high risk of developing cardiovascular disease. This includes diabetic cardiomyopathy (DbCM), a condition characterized by left ventricular diastolic dysfunction that is often present in individuals with pre- or early-stage T2D. Although there are numerous mediators that contribute to the development of DbCM, perturbations in cardiac substrate metabolism are widely believed to play a major role in its pathogenesis. In particular, myocardial glucose oxidation is often suppressed due to decreased activity of the pyruvate dehydrogenase (PDH) complex, the rate-limiting enzyme of glucose oxidation, which is responsible for decarboxylating pyruvate to acetyl CoA, thus acting as the link between glycolysis and oxidative phosphorylation of glucose. Importantly, numerous preclinical studies suggest that restoring suppressed myocardial glucose oxidation can alleviate DbCM. In this review, we will describe the major perturbations that characterize myocardial substrate metabolism in T2D, while discussing the primary pharmacological approaches that have been pursued to stimulate myocardial PDH activity and glucose oxidation. We will also highlight potential mechanisms explaining how increasing myocardial PDH activity and glucose oxidation favorably influence diastolic function. Given the increasing prevalence of DbCM in the human population, it is not only imperative to better understand its pathophysiology but also to develop novel therapies for its management, which may also have utility in the management of heart failure with preserved ejection fraction.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".