Retinoic acid receptor signaling is required to maintain glucose‐stimulated insulin secretion and β‐cell mass
Bibliographic record
Abstract
ABSTRACT Retinoic acid signaling is required for maintaining a range of cellular processes, including cell differentiation, proliferation, and apoptosis. We investigated the actions of all‐ trans ‐retinoic acid (atRA) signaling in pancreatic β‐cells of adult mice. atRA signaling was ablated in β‐cells by overexpressing a dominant‐negative retinoic acid receptor (RAR)‐α mutant (RARdn) using an inducible Cre‐Lox system under the control of the pancreas duodenal homeobox gene promoter. Our studies establish that hypomorphism for RAR in β‐cells leads to an age‐dependent decrease in plasma insulin in the fed state and in response to a glucose challenge. Glucose‐stimulated insulin secretion was also impaired in islets isolated from mice expressing RARdn. Among genes that are atRA responsive, Glut2 and Gck mRNA levels were decreased in isolated islets from RARdn‐expressing mice. Histologic analyses of RARdn‐expressing pancreata revealed a decrease in β‐cell mass and insulin per β‐cell 1 mo after induction of the RARdn. Our results indicate that atRA signaling mediated by RARs is required in the adult pancreas for maintaining both β‐cell function and mass, and provide insights into molecular mechanisms underlying these actions.—Brun, P.‐J., Grijalva, A., Rausch, R., Watson, E., Yuen, J. J., Das, B. C., Shudo, K., Kagechika, H., Leibel, R. L., Blaner, W. S. Retinoic acid receptor signaling is required to maintain glucose‐stimulated insulin secretion and β‐cell mass. FASEB J . 29, 671‐683 (2015). www.fasebj.org
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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) | 0.000 | 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".