Induction of proximal tubular proliferation and lengthening in response to sodium glucose linked cotransporter‐2 inhibition in experimental rats
Bibliographic record
Abstract
AIMS/INTRODUCTION: While SGLT2 accounts for >90% of kidney glucose reabsorption, its pharmacological inhibition or genetic knockdown reduces glucose reabsorption by only 50%. MATERIALS AND METHODS: We postulated that the less than expected glucosuric response to SGLT2 inhibition might result from a compensatory increase in the length of the proximal tubule as seen in experimental diabetes where early tubular proliferation is followed by tubular lengthening. Taking advantage of their differing anatomical locations, stereological techniques were used to differentiate the SGLT1 expressing straight proximal tubule that lies within the outer stripe of the outer medulla (S3 segment) and that of the predominantly SGLT2 expressing early proximal convoluted tubule located within the kidney cortex (S1, S2 segments). RESULTS: The SGLT2 inhibitor, dapagliflozin, induced an early, transient hyperplastic response (3-fold increase of Ki67 labelling, P < 0.0001) in S3 proximal tubular cells followed by a 32% increase in its length (P < 0.0001). In contrast, the length of the SGLT2 expressing S1, S2 segments of the proximal tubule was unaffected. CONCLUSIONS: The finding that SGLT2 inhibition leads to expansion of the S3 segment of the proximal tubule, the site of SGLT1, is suggestive of a physiological response to diminish urinary glucose loss akin to that occurring in experimental diabetes. These findings provide a cogent explanation for the less-thanthan-expected effect of this drug class on glucose reabsorption.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".