Abstract
Background: The mechanochemical enzyme dynamin mediates endocytosis and regulates neuroendocrine cell exocytosis. Enteroendocrine L cells co-secrete the anorectic gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) postprandially and is a potential therapeutic target for metabolic diseases. In the present study, we aimed to determine if dynamin is implicated in human L cell secretion. Methods: Western blot was performed on the murine L cell line GLUTag. Static incubation of human colonic mucosae with activators and inhibitors of dynamin was carried out. GLP-1 and PYY contents of the secretion supernatants were assayed using ELISA. Results and conclusion: s: Both dynamin I and II are expressed in GLUTag cells. The dynamin activator Ryngo 1–23 evoked significant GLP-1 and PYY release from human colonic mucosae while the dynamin inhibitor Dynole 3–42 significantly inhibited release triggered by known L cell secretagogues. Thus, the cell signaling regulator dynamin is able to bi-directionally regulate L cell hormone secretion in the human gut and may represent a novel target for gastrointestinal-targeted metabolic drug development.
| Original language | English |
|---|---|
| Article number | 111398 |
| Number of pages | 5 |
| Journal | MOLECULAR AND CELLULAR ENDOCRINOLOGY |
| Volume | 535 |
| DOIs | |
| Publication status | Published - 15 Sept 2021 |
| Externally published | Yes |
Keywords
- Dynamin
- Enteroendocrine cells
- GLP-1
- Gut hormones
- PYY