A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion
Nat Commun. 2024-08-13; 15(1):
DOI: 10.1038/s41467-024-51076-4
Lire sur PubMed
Montaner M(1), Denom J(1), Simon V(2), Jiang W(3), Holt MK(3)(4), Brierley
DI(3), Rouch C(1), Foppen E(5)(6), Kassis N(1), Jarriault D(7), Khan D(8),
Eygret L(7), Mifsud F(1), Hodson DJ(9), Broichhagen J(10), Van Oudenhove L(11),
Fioramonti X(7), Gault V(8), Cota D(2), Reimann F(12), Gribble FM(12),
Migrenne-Li S(1), Trapp S(13), Gurden H(#)(14), Magnan C(#)(15).
Author information:
(1)Université Paris Cité, Unit of Functional and Adaptive Biology (BFA), UMR
8251 CNRS, Paris, France.
(2)University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux,
France.
(3)Centre for Cardiovascular and Metabolic Neuroscience, Department of
Neuroscience, Physiology & Pharmacology, UCL, London, UK.
(4)School of Life Sciences, University of Warwick, Coventry, UK.
(5)Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience
(NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences
(KNAW), Amsterdam, Netherlands.
(6)Laboratory of Endocrinology, Amsterdam UMC, Amsterdam Gastroenterology
Endocrinology Metabolism (AGEM), Amsterdam, Netherlands.
(7)University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux,
France.
(8)Faculty of Life and Health Sciences, School of Biomedical Sciences, Ulster
University, Coleraine, UK.
(9)University of Oxford, Oxford Centre for Diabetes, Endocrinology and
Metabolism (OCDEM), Oxford, UK.
(10)Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin,
Germany.
(11)Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research in
Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and
Metabolism (CHROMETA), University of Leuven, Leuven, Belgium.
(12)Institute of Metabolic Science & MRC Metabolic Diseases Unit, University of
Cambridge, Cambridge, UK.
(13)Centre for Cardiovascular and Metabolic Neuroscience, Department of
Neuroscience, Physiology & Pharmacology, UCL, London, UK. .
(14)Université Paris Cité, Unit of Functional and Adaptive Biology (BFA), UMR
8251 CNRS, Paris, France. .
(15)Université Paris Cité, Unit of Functional and Adaptive Biology (BFA), UMR
8251 CNRS, Paris, France. .
(#)Contributed equally
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.
© 2024. The Author(s).
DOI: 10.1038/s41467-024-51076-4
PMCID: PMC11322178
PMID: 39138162 [Indexed for MEDLINE]
Conflict of interest statement: J.B. and D.J.H. receive licensing revenue from
Celtarys Research. All other authors declare that they have no known competing
financial interests or personal relationships that could have appeared to
influence the work reported in this paper.