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A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

Authors :
Mireia Montaner
Jessica Denom
Vincent Simon
Wanqing Jiang
Marie K. Holt
Daniel I. Brierley
Claude Rouch
Ewout Foppen
Nadim Kassis
David Jarriault
Dawood Khan
Louise Eygret
Francois Mifsud
David J. Hodson
Johannes Broichhagen
Lukas Van Oudenhove
Xavier Fioramonti
Victor Gault
Daniela Cota
Frank Reimann
Fiona M. Gribble
Stephanie Migrenne-Li
Stefan Trapp
Hirac Gurden
Christophe Magnan
Source :
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.b3515a89fa242b4a3b002d0b2c03c19
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-024-51076-4