β-Cell <i>Pdx1</i> Expression Is Essential for the Glucoregulatory, Proliferative, and Cytoprotective Actions of Glucagon-Like Peptide-1
Bibliographic record
Abstract
Glucagon-like peptide-1 (GLP-1) regulates energy intake, gastrointestinal motility, and nutrient disposal. The relative importance of the islet beta-cell for GLP-1 actions remains unclear. We determined the role of the islet beta-cell and the pancreatic duodenal homeobox-1 (Pdx1) transcription factor for GLP-1 receptor (GLP-1R)-dependent actions through analysis of mice with beta-cell-specific inactivation of the Pdx1 gene (beta-cell(Pdx1-/-) mice). The GLP-1R agonist exendin-4 (Ex-4) reduced glycemic excursion following intraperitoneal (i.p.) glucose challenge in control littermates (beta-cell(Pdx1+/+) mice) but not in beta-cell(Pdx1-/-) mice. Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice. Furthermore, Ex-4 significantly increased beta-cell proliferation and reduced beta-cell apoptosis in beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) mice. Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets. Surprisingly, Ex-4 failed to reduce levels of plasma glucagon in beta-cell(Pdx1-/-) mice. These findings demonstrate that Pdx1 expression is essential for integrating GLP-1R-dependent signals regulating alpha-cell glucagon secretion and for the growth, differentiated function, and survival of islet beta-cells.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".