Validation and Mechanistic Studies of Gluconeogenesis Regulators Identified from Zebrafish Chemical Genetic Screens
Bibliographic record
Abstract
Phosphoenolypyruvate carboxykinase (PEPCK) is the rate limiting enzyme in hepatic gluconeogenesis, which produces glucose from pyruvate to maintain circulating glucose level according to the bodyâ s needs. Cytosolic PEPCK (pck1) is widely studied for its crucial role in hepatic gluconeogenesis. High levels of pck1 are associated with the development of type 2 diabetes; conversely, improved insulin sensitivity is observed in mice with decreased pck1 level. Ten potential lead compounds from previous screening of 727 FDA-approved compounds were examined using pck1 zebrafish reporter lines, Tg(pck1:luc2) and Tg(pck1:Venus). Compounds were tested in larval zebrafish and ranked based on their ability to regulate pck1 expression and glucose levels. Subsequently, a diabetic mouse model was used to further validate the potential anti-hyperglycemic effects of the selected compound (Esomeprazole, Eso). Eso treatment improved glucose homeostasis in diabetic mice as determined by pyruvate tolerance tests. Here we describe a possible mechanism of action of Eso, which involves regulation of hepatic gluconeogenesis through insulin-dependent down-regulation of pck1.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.003 | 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".