THU263 Intestinal Production of H(2)S And Its Regulation Of GLP-2

Disclosure: J. Hammond: None. G. Yang: None. J. Gagnon: None. Background: Hydrogen sulfide (H(2)S) is an endogenously produced gasotransmitter that regulates a variety of physiological processes including hormone regulation. In individuals with Crohn’s disease or colitis, H(2)S is elevated. Whether this H(2)S 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 H(2)S in the regulation of glucagon-like peptides. Hypothesis: We hypothesize that local H(2)S 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 H(2)S injections or lacking the H(2)S-producing enzyme cystathionine gamma-lyase (CSE). Additionally, H(2)S production and GLP-2 secretion were examined from mouse enteroendocrine L-cells (GLUTag). Results: CSE KO mice had significantly reduced intestinal H(2)S production. A slight increase in circulating GLP-2 was found in CSE KO mice. H(2)S was also produced directly from enteroendocrine cells which was partially blocked using CSE enzyme inhibitors. When enteroendocrine L-cells were treated with H(2)S 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 H(2)S 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 H(2)S, and that H(2)S donors can suppress GLP-2 secretion. These findings suggest that GLP-2 may play a role in the interplay between H(2)S and gastric health. These results could provide support for the potential use of H(2)S drugs in the treatment of GI diseases. Presentation: Thursday, June 15, 2023