A Neuronal Circuit Driven by GLP-1 in the Olfactory Bulb Regulates Insulin Secretion

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Aug 13

PMID 39138162

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

Affiliations

Soon will be listed here.

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 α-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABA 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.

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