THU263 Intestinal Production of H2S And Its Regulation Of GLP-2
Bibliographic record
Abstract
Abstract Disclosure: J. Hammond: None. G. Yang: None. J. Gagnon: None. Background: Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter that regulates a variety of physiological processes including hormone regulation. In individuals with Crohn’s disease or colitis, H2S is elevated. Whether this H2S plays a role in gut disease development or protection is not clear. Glucagon-Like Peptide-2 (GLP-2) is a gut health-promoting peptide hormone produced in the enteroendocrine L-cells located primarily in the distal GI tract. In the gut, GLP-2 increases cell proliferation, enhances barrier function, and decreases inflammation. Furthermore, GLP-2 administration has been shown to be protective in both Crohn’s and Colitis. Finally, our previous work has shown a role for H2S in the regulation of glucagon-like peptides. Hypothesis: We hypothesize that local H2S production in the distal GI tract and in enteroendocrine cells can regulate GLP-2 secretion and downstream gut physiology.Methods: GLP-2 secretion and gut physiology were examined in mice receiving exogenous H2S injections or lacking the H2S-producing enzyme cystathionine gamma-lyase (CSE). Additionally, H2S production and GLP-2 secretion were examined from mouse enteroendocrine L-cells (GLUTag). Results: CSE KO mice had significantly reduced intestinal H2S production. A slight increase in circulating GLP-2 was found in CSE KO mice. H2S was also produced directly from enteroendocrine cells which was partially blocked using CSE enzyme inhibitors. When enteroendocrine L-cells were treated with H2S donors (NaHS and GYY 4137), GLP-2 secretion was significantly reduced (with no effect on cell viability). Ongoing work will explore the direct effects of H2S administration in mice on circulating GLP-2, and any changes that occur in the gut epithelium as a result. Discussion/Conclusions: Our work indicates that the enteroendocrine cell can produce the gasotransmitter H2S, and that H2S donors can suppress GLP-2 secretion. These findings suggest that GLP-2 may play a role in the interplay between H2S and gastric health. These results could provide support for the potential use of H2S drugs in the treatment of GI diseases. Presentation: Thursday, June 15, 2023
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".