Year: 2024
Type: article
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. The regulation of energy homeostasis by centrally-produced GLP-1 is not yet fully understood. Here, authors show that GLP-1 neuronal circuitry in the olfactory bulb reduces food intake and enhances insulin secretion in obese mice. The increase in insulin secretion is mediated by a GABA-dependent relay in the paraventricular hypothalamus and decreased sympathetic nerve activity.
Source: Nature Communications
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
Institutions: Centre National de la Recherche Scientifique, Université Paris Cité, Unit of Functional and Adaptive Biology, Université de Bordeaux, Inserm, Neurocentre Magendie, University College London, University of Warwick, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam University Medical Centers, Amsterdam Gastroenterology Endocrinology Metabolism, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, NutriNeuro, Institut Polytechnique de Bordeaux, University of Ulster, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, KU Leuven, University of Cambridge, Wellcome/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: Wellcome Trust, UK Research and Innovation, British Heart Foundation, Diabetes UK, European Foundation for the Study of Diabetes, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, KU Leuven, China Scholarship Council, Centre National de la Recherche Scientifique, Université de Paris, Medical Research Council, Engineering and Physical Sciences Research Council, Bijzonder Onderzoeksfonds UGent
Awards: G1045075726, Investigating the role of immature beta cells in insulin release from the intact islet, Targeting the gut in metabolic disease, Functional mapping of gut-brain neurocircuitry in health and obesity, Analysis of the brain GLP-1 circuitry at cellular level to characterise its roles in the control of food intake, G2450198060, G271718852, G3105419033, Neural circuits of glucagon-like peptide-1 (GLP-1) action in health and disease, Dissecting the role of caudal brainstem corticotropin-releasing hormone signalling and preproglucagon neurons in anxiety- related sympathoexcitation, Role of the POMC-ventral striatal neurocircuit in the development of diet-induced obesity, G381665449, Functional mapping of gut-brain neurocircuitry in health and obesity, Linking GPCR organization states with functional heterogeneity in the pancreatic islet, Exploring beta cell reprogramming by glucocorticoids, G6823783208, G7240651115, G7777646733, G8127307188, G8128783587, G8234668411, G8286074132, Targeting the gut in metabolic disease, G8995835327, G905023109
OpenAlex ID: W4401546168