Dynamin regulates L cell secretion in human gut. (15th September 2021)

• Record Type: Journal Article
• Authors: Sun, Emily WL.; Matusica, Dusan; Wattchow, David A.; McCluskey, Adam; Robinson, Philip J.; Keating, Damien J.
• Is Part Of: Molecular and cellular endocrinology. Volume 535(2021)
• Publication Date: 2021-09-15
• Subjects: Dynamin -- Enteroendocrine cells -- GLP-1 -- PYY -- Gut hormones; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2021.111398
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: Both isoforms of dynamin are expressed in the murine L cell line GLUTag. The dynamin activator Ryngo 1–23 evokes significant GLP-1 and PYY release from human colonic mucosae. The dynamin inhibitor Dynole 3–42 significantly inhibits release triggered by known L cell secretagogues.