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Dynamin regulates L cell secretion in human gut.

Emily Wl Sun1, Dusan Matusica1, David A Wattchow2

  • 1Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, Australia.

Molecular and Cellular Endocrinology
|July 18, 2021
PubMed
Summary

Dynamin regulates gut hormone secretion. This study shows dynamin bi-directionally controls glucagon-like peptide 1 and peptide YY release from human L cells, suggesting a new metabolic disease target.

Keywords:
DynaminEnteroendocrine cellsGLP-1Gut hormonesPYY

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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.