The contribution of phosphodiesterases to cardiac dysfunction in rats with metabolic syndrome induced by a high-carbohydrate diet
Bibliographic record
Abstract
Metabolic syndrome (MetS) is a cluster of risk factors, including insulin resistance among others, underlying the development of diabetes and (or) cardiovascular diseases. Studies show a close relationship between cardiac dysfunction and abnormal cAMP catabolism, which contributes to pathological remodelling. Stimulating the synthesis of cAMP via suppression of phosphodiesterases (PDEs) has positive therapeutic effects. Therefore, we examined the role of PDEs on cardiac dysfunction in high-carbohydrate diet-induced MetS rats. We first demonstrated significantly high expression levels of PDE3 and PDE4, the most highly expressed subtypes, together with depressed cAMP levels in heart tissue from MetS rats. Second, we demonstrated the activity of these PDEs by using either their basal or PDE inhibitor-induced intracellular levels of cAMP and Ca2+, the transient intracellular Ca2+ changes under electrical stimulation, isometric contractions in papillary muscle strips and some key signalling proteins (such as RyR2, PLN, PP1A, and PKA) are responsible for the Ca2+ homeostasis in isolated cardiomyocytes from MetS rats. The clear recovery in decreased basal cAMP levels, increased protein expression levels of PDE3 and PDE4, and positive responses in the altered Ca2+ homeostasis to PDE inhibitors as seen in our study can provide important insights about the roles of activated PDEs in depressed contractile activity in hearts from MetS rats.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".