Reduction in IL-33 expression exaggerates ischaemia/reperfusion-induced myocardial injury in mice with diabetes mellitus
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Bibliographic record
Abstract
AIMS: The underlying mechanism(s) of vulnerability of the diabetic myocardium to ischaemia/reperfusion (I/R)-induced injury is not fully understood. Interleukin-33 (IL-33) has been reported showing the beneficial effect to the myocardium on I/R injury. The aims of this study were to test whether diabetes mellitus (DM) affects myocardial levels of IL-33 and to examine whether reduction in IL-33 is responsible for exaggerated I/R injury in the diabetic myocardium. METHODS AND RESULTS: DM hearts were challenged with I/R in vivo, whereas while isolated cardiomyocytes in vitro were conditioned with high glucose (HG) followed by an anoxia/reoxygenation (A/R) challenge. Myocardial levels of IL-33 were decreased in mice with DM which was associated with increased protein kinase C βII (PKCβII) activation. Exogenous IL-33 prevented the DM-induced PKCβII activation and attenuated I/R injuries (myocardial infarction size and apoptosis). HG-conditioned myocytes incurred exaggerated apoptosis when compared with naïve myocytes after A/R which was attenuated by IL-33. HG activated PKCβII in cardiomyocytes, which was further enhanced by A/R. IL-33 prevented the PKCβII activation in myocytes with HG or HG and A/R. Inhibition of PKCβII prevented the beneficial effect of IL-33. Finally, IL-33 up-regulated diacylglycerol kinase zeta (DGK-zeta) in cardiomyocytes and reversed the down-regulation of myocardial DGK-zeta in mice with DM. CONCLUSION: Our results indicate that decreased levels of IL-33 are responsible for the increased sensitivity of the myocardium to I/R in DM. Reduction in IL-33 results in a chronic activation of PKCβII. I/R further enhances PKCβII activation in the diabetic myocardium which results in exaggeration of myocardial injury.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it