Dynamin regulates L cell secretion in human gut

Emily WL. Sun, Dusan Matusica, David A. Wattchow, Adam McCluskey, Philip J. Robinson, Damien J. Keating

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number111398
Number of pages5
JournalMOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume535
DOIs
Publication statusPublished - 15 Sep 2021
Externally publishedYes

Keywords

  • Dynamin
  • Enteroendocrine cells
  • GLP-1
  • Gut hormones
  • PYY

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