Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events

Ayoze González-Santana; Judith Estévez-Herrera; Elizabeth P Seward; Ricardo Borges; José David Machado

doi:10.1016/j.celrep.2021.109609

Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events

Cell Rep. 2021 Aug 24;36(8):109609. doi: 10.1016/j.celrep.2021.109609.

Authors

Ayoze González-Santana¹, Judith Estévez-Herrera¹, Elizabeth P Seward², Ricardo Borges¹, José David Machado³

Affiliations

¹ Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain.
² Department of Biomedical Science, Firth Court, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
³ Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain. Electronic address: david.machado@ull.edu.es.

PMID: 34433018
DOI: 10.1016/j.celrep.2021.109609

Abstract

Agonists for glucagon-like-peptide-1 receptor (GLP-1R) are currently used for the treatment of type 2 diabetes and obesity. Their benefits have been centered on pancreas and hypothalamus, but their roles in other organ systems are not well understood. We studied the action of GLP-1R on secretions of adrenal medulla. Exendin-4, a synthetic analog of GLP-1, increases the synthesis and the release of catecholamines (CAs) by increasing cyclic AMP (cAMP) production, without apparent participation of cAMP-regulated guanine nucleotide exchange factor (Epac). Exendin-4, when incubated for 24 h, increases CA synthesis by promoting the activation of tyrosine hydroxylase. Short incubation (20 min) increases the quantum size of exocytotic events by switching exocytosis from partial to full fusion. Our results give a strong support to the role of GLP-1 in the fine control of exocytosis.

Keywords: GLP-1; adrenal; adrenaline; amperometry; cAMP; chromogranin A; exocytosis; secretion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chromaffin Cells / drug effects
Chromaffin Cells / metabolism*
Cyclic AMP / metabolism
Diabetes Mellitus, Type 2 / metabolism
Exenatide / metabolism
Exenatide / pharmacology*
Exocytosis / drug effects
Exocytosis / physiology
Glucagon-Like Peptide 1 / metabolism*
Glucagon-Like Peptide-1 Receptor / drug effects*
Glucagon-Like Peptide-1 Receptor / metabolism
Guanine Nucleotide Exchange Factors / drug effects
Guanine Nucleotide Exchange Factors / metabolism
Islets of Langerhans / drug effects
Islets of Langerhans / metabolism
Rats
Receptors, Glucagon / drug effects
Receptors, Glucagon / metabolism

Substances

Glucagon-Like Peptide-1 Receptor
Guanine Nucleotide Exchange Factors
Receptors, Glucagon
Glucagon-Like Peptide 1
Exenatide
Cyclic AMP