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

Author

Listed:
  • Mireia Montaner

    (UMR 8251 CNRS)

  • Jessica Denom

    (UMR 8251 CNRS)

  • Vincent Simon

    (U1215)

  • Wanqing Jiang

    (UCL)

  • Marie K. Holt

    (UCL
    University of Warwick)

  • Daniel I. Brierley

    (UCL)

  • Claude Rouch

    (UMR 8251 CNRS)

  • Ewout Foppen

    (An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW)
    Amsterdam Gastroenterology Endocrinology Metabolism (AGEM))

  • 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)

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.

Suggested Citation

  • 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 & Fran, 2024. "A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51076-4
    DOI: 10.1038/s41467-024-51076-4
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    References listed on IDEAS

    as
    1. J. Nicholas Betley & Shengjin Xu & Zhen Fang Huang Cao & Rong Gong & Christopher J. Magnus & Yang Yu & Scott M. Sternson, 2015. "Neurons for hunger and thirst transmit a negative-valence teaching signal," Nature, Nature, vol. 521(7551), pages 180-185, May.
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