Dynamin regulates L cell secretion in human gut

Area of Science:

• Cell Biology
• Endocrinology
• Gastroenterology

Background:

• Dynamin is a mechanochemical enzyme crucial for endocytosis and regulating neuroendocrine cell exocytosis.
• Enteroendocrine L cells co-secrete glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), hormones targeted for metabolic disease therapies.
• The role of dynamin in human L cell secretion remained undetermined.

Purpose of the Study:

• To investigate the implication of dynamin in human L cell secretion.
• To determine if dynamin can modulate the release of GLP-1 and PYY.

Main Methods:

• Western blot analysis of dynamin expression in the murine L cell line GLUTag.
• Incubation of human colonic mucosae with dynamin activators (Ryngo 1-23) and inhibitors (Dynole 3-42).
• Quantification of GLP-1 and PYY in secretion supernatants using ELISA.

Main Results:

• Dynamin I and II were detected in GLUTag cells.
• The dynamin activator Ryngo 1-23 significantly increased GLP-1 and PYY release from human colonic mucosae.
• The dynamin inhibitor Dynole 3-42 significantly suppressed L cell secretagogue-induced hormone release.

Conclusions:

• Dynamin bi-directionally regulates L cell hormone secretion in the human gut.
• Dynamin's role in modulating GLP-1 and PYY release positions it as a potential novel therapeutic target for metabolic diseases.
• Targeting dynamin could offer a new strategy for gastrointestinal-targeted metabolic drug development.