SP374CANAGLIFLOZIN, A SODIUM-GLUCOSE CO-TRANSPORTER 2 (SGLT-2) BLOCKER, NORMALIZES BLOOD GLUCOSE WITHOUT AFFECTING SYSTEMIC BLOOD PRESSURE, OXIDATIVE STRESS, INTRARENAL ANGIOTENSINOGEN GENE EXPRESSION AND KIDNEY INJURY IN TYPE 1 DIABETIC MICE
Bibliographic record
Abstract
Introduction and Aims: We investigated the impact of the SGLT-2 blocker, canagliflozin, on blood glucose, systolic blood pressure (SBP), glomerular filtration rate (GFR), urinary albumin/creatinine ratio (ACR), renal oxidative stress, angiotensinogen (Agt, the sole precursor all angiotensins) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression in type 1 diabetes in Akita mice. Methods: Adult male Akita mice (aged 12 weeks) were treated +/- canagliflozin (0.3 mg/ml in drinking water) and euthanized at week 16. Blood glucose and SBP were monitored weekly in Akita mice and sex-matched non-Akita littermates (controls). At week 16, GFR and ACR were measured, and kidneys were processed for histology and analysis of oxidative stress. Gene and protein expression in isolated renal proximal tubules (RPT) were evaluated by real time-qPCR and Western blotting, respectively. Urinary Agt and angiotensin II (Ang II) levels were quantified by ELISA. Rat immortalized RPTCs were also studied. Results: As anticipated, Akita mice developed hyperglycemia, elevated SBP, renal hypertrophy and ACR. Canagliflozin treatment normalized blood glucose but did not affect SBP, renal hypertrophy and ACR in Akita mice. Tubular oxidative stress, expression of Agt and Nrf2 in RPT and urinary Agt and Ang II levels were also significantly increased in Akita mice, but canagliflozin treatment did not reverse these changes. In vitro, canagliflozin did not prevent the stimulatory effect high glucose on Agt and Nrf2 gene expression in rat RPTCs.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".