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

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 Oudenhove, Xavier Fioramonti, Victor Gault, Daniela Cota, Frank Reimann, Fiona M. Gribble, Stephanie Migrenne-Li, Stefan Trapp (), Hirac Gurden () and Christophe Magnan ()
Additional contact information
Mireia Montaner: UMR 8251 CNRS
Jessica Denom: UMR 8251 CNRS
Vincent Simon: U1215
Wanqing Jiang: UCL
Marie K. Holt: UCL
Daniel I. Brierley: UCL
Claude Rouch: UMR 8251 CNRS
Ewout Foppen: An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW)
Nadim Kassis: UMR 8251 CNRS
David Jarriault: UMR 1286
Dawood Khan: School of Biomedical Sciences, Ulster University
Louise Eygret: UMR 1286
Francois Mifsud: UMR 8251 CNRS
David J. Hodson: Endocrinology and Metabolism (OCDEM)
Johannes Broichhagen: Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
Lukas Oudenhove: University of Leuven
Xavier Fioramonti: UMR 1286
Victor Gault: School of Biomedical Sciences, Ulster University
Daniela Cota: U1215
Frank Reimann: University of Cambridge
Fiona M. Gribble: University of Cambridge
Stephanie Migrenne-Li: UMR 8251 CNRS
Stefan Trapp: UCL
Hirac Gurden: UMR 8251 CNRS
Christophe Magnan: UMR 8251 CNRS

Nature Communications, 2024, vol. 15, issue 1, 1-14

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.

Date: 2024
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DOI: 10.1038/s41467-024-51076-4

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