A sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin comparison with insulin shows important effects on Zn<sup>2+</sup>-transporters in cardiomyocytes from insulin-resistant metabolic syndrome rats through inhibition of oxidative stress
Bibliographic record
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed significant effects in patients with diabetes or metabolic syndrome (MetS) with high cardiovascular risk. Although the increased intracellular Zn2+ level ([Zn2+]i), oxidative stress, and altered cardiac matrix metalloproteinases (MMPs) in diabetic cardiomyopathy can intersect with different signaling pathways, the exact mechanisms are not known yet. Since either MMPs or SGLT2 have important roles in cardiac-fibrosis under hyperglycemia, we aimed to examine the role of SGLT2 inhibitor dapagliflozin (DAP) on cardiac Zn2+-transporters responsible for [Zn2+]i-regulation, comparison to insulin (INS), together with MMP levels and systemic oxidative stress status in MetS-rats. High-carbohydrated diet-induced MetS-rats received DAP or INS for 2 weeks. DAP but not INS in MetS-rats significantly decreased high blood-glucose levels, while both treatments exerted benefits on increased total oxidative status and decreased total antioxidant status in MetS-rat plasma as well as in heart tissue. Protein levels of Zn2+-transporters, responsible for Zn2+-influx into cytosol, ZIP7 and ZIP14 were increased with significant decrease in ZIP8 of MetS-rat cardiomyoctes, while Zn2+-transporters, responsible for cytosolic Zn2+-efflux, ZnT7 was decreased with no change in ZnT8. Both treatments induced significant beneficial effects on altered ZIP14, ZIP8, and ZnT7 levels. Furthermore, both treatments exerted benefits on depressed gelatin-zymography and protein expression levels of MMP-2 and MMP-9 in MetS-rat ventricular cardiomyocytes. The direct effect of DAP on heart was also confirmed with measurements of left ventricular developed pressure. Overall, we showed that DAP has important antioxidant-like cardio-protective effects in MetS-rats, similar to INS-effect, affecting Zn2+-regulation via Zn2+-transporters, MMPs, and oxidative stress. Therefore one can suggest that SGLT2 inhibitors can be new therapeutic agents for cardio-protection not only in hyperglycemia but also in failing heart.
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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) | 0.001 | 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 | 0.001 |
| 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".