Ontogeny of the Glucagon-Like Peptide-2 Receptor Axis in the Developing Rat Intestine**This work was supported in part by operating grants from the Medical Research Council (to D.J.D. and P.L.B.), the Crohn’s and Colitis Foundation of Canada (to P.L.B.), and the Ontario Research and Development Challenge Fund (to D.J.D.). GLP-2 is the subject of a licensing agreement between Toronto General Hospital, the University of Toronto, D.J.D., and NPS Allelix Corp.
Bibliographic record
Abstract
Glucagon-like peptide-2 (GLP-2) is secreted by enteroendocrine cells in the small and large intestines and exerts intestinotropic effects in the gastrointestinal mucosal epithelium of the adult rodent. The actions of GLP-2 are mediated by the GLP-2 receptor, a new member of the G protein-coupled receptor superfamily. To ascertain whether the GLP-2/GLP-2 receptor axis is expressed and functional in the developing intestine, we have studied the synthesis of GLP-2 and the expression of the GLP-2 receptor (GLP-2R) in the fetal and neonatal rat gut. GLP-2 immunoreactivity (GLP-2-IR) was detected in the fetal rat intestine, and fetal rat intestinal cell cultures secreted correctly processed GLP-2(1-33) into the medium. High levels of GLP-2(1-33) were also detected in the circulation of 13-day-old neonatal rats (P < 0.001 vs. adult). Analysis of GLP-2 receptor expression by RT-PCR demonstrated GLP-2R messenger RNA transcripts in fetal intestine and in neonatal stomach, jejunum, ileum, and colon. The levels of GLP-2R messenger RNA transcripts were comparatively higher in the fetal and neonatal intestine (P < 0.05-001 vs. adult) and declined to adult levels by postnatal day 21. Subcutaneous administration of a degradation-resistant GLP-2 analog, h[Gly2]-GLP-2 once daily for 10 days increased stomach (0.009 +/- 0.0003 vs. 0.007 +/- 0.002 g/g body mass, h[Gly2]-GLP-2-treated vs. controls; P < 0.05) and small bowel weight (0.043 +/- 0.0037 vs. 0.031 +/- 0.0030 g/g body mass; P < 0.05). h[Gly2]-GLP-2 also increased both small (2.4 +/- 0.05 vs. 1.8 +/- 0.17 cm/g body mass; P < 0.05) and large bowel length (0.32 +/- 0.01 vs. 0.25 +/- 0.02 cm/g body mass, h[Gly2]-GLP-2-treated vs. saline-treated controls, respectively; P < 0.05) in neonatal rats. These findings demonstrate that both components of the GLP-2/GLP-2 receptor axis are expressed in the fetal and neonatal intestine. The ontogenic regulation and functional integrity of this axis raises the possibility that GLP-2 may play a role in the development and/or maturation of the developing rat intestine.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| 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".