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 Van  Oudenhove; Xavier  Fioramonti; Victor A Gault; Daniela  Cota; Frank  Reimann; Fiona M.  Gribble; Stephanie  Migrenne-Li; Stefan  Trapp; Hirac  Gurden; Christophe  Magnan

doi:10.1038/s41467-024-51076-4

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 Van Oudenhove, Xavier Fioramonti, Victor A Gault, Daniela Cota, Frank Reimann Fiona M. Gribble, Stephanie Migrenne-Li, Stefan Trapp, Hirac Gurden, Christophe Magnan

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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.

Original language	English
Article number	6941
Pages (from-to)	1-14
Number of pages	14
Journal	Nature Communications
Volume	15
Issue number	1
Early online date	13 Aug 2024
DOIs	https://doi.org/10.1038/s41467-024-51076-4
Publication status	Published online - 13 Aug 2024

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Publisher Copyright:
© The Author(s) 2024.

Keywords

Neural circuits
Obesity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Montaner, M., Denom, J., Simon, V., Jiang, W., Holt, M. K., Brierley, D. I., Rouch, C., Foppen, E., Kassis, N., Jarriault, D., Khan, D., Eygret, L., Mifsud, F., Hodson, D. J., Broichhagen, J., Oudenhove, L. V., Fioramonti, X., Gault, V. A., Cota, D., ... Magnan, C. (2024). A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion. Nature Communications, 15(1), 1-14. Article 6941. Advance online publication. https://doi.org/10.1038/s41467-024-51076-4

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title = "A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion",

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.",

keywords = "Neural circuits, Obesity",

author = "Mireia Montaner and Jessica Denom and Vincent Simon and Wanqing Jiang and Holt, {Marie K.} and Brierley, {Daniel I.} and Claude Rouch and Ewout Foppen and Nadim Kassis and David Jarriault and Dawood Khan and Louise Eygret and Francois Mifsud and Hodson, {David J.} and Johannes Broichhagen and Oudenhove, {Lukas Van} and Xavier Fioramonti and Gault, {Victor A} and Daniela Cota and Frank Reimann and Gribble, {Fiona M.} and Stephanie Migrenne-Li and Stefan Trapp and Hirac Gurden and Christophe Magnan",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = aug,

day = "13",

doi = "10.1038/s41467-024-51076-4",

language = "English",

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Montaner, M, Denom, J, Simon, V, Jiang, W, Holt, MK, Brierley, DI, Rouch, C, Foppen, E, Kassis, N, Jarriault, D, Khan, D, Eygret, L, Mifsud, F, Hodson, DJ, Broichhagen, J, Oudenhove, LV, Fioramonti, X, Gault, VA, Cota, D, Reimann, F, Gribble, FM, Migrenne-Li, S, Trapp, S, Gurden, H & Magnan, C 2024, 'A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion', Nature Communications, vol. 15, no. 1, 6941, pp. 1-14. https://doi.org/10.1038/s41467-024-51076-4

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AU - Montaner, Mireia

AU - Denom, Jessica

AU - Simon, Vincent

AU - Jiang, Wanqing

AU - Holt, Marie K.

AU - Brierley, Daniel I.

AU - Rouch, Claude

AU - Foppen, Ewout

AU - Kassis, Nadim

AU - Jarriault, David

AU - Khan, Dawood

AU - Eygret, Louise

AU - Mifsud, Francois

AU - Hodson, David J.

AU - Broichhagen, Johannes

AU - Oudenhove, Lukas Van

AU - Fioramonti, Xavier

AU - Gault, Victor A

AU - Cota, Daniela

AU - Reimann, Frank

AU - Gribble, Fiona M.

AU - Migrenne-Li, Stephanie

AU - Trapp, Stefan

AU - Gurden, Hirac

AU - Magnan, Christophe

PY - 2024/8/13

Y1 - 2024/8/13

N2 - 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.

AB - 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.

KW - Neural circuits

KW - Obesity

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U2 - 10.1038/s41467-024-51076-4

DO - 10.1038/s41467-024-51076-4

M3 - Article

C2 - 39138162

SN - 2041-1723

VL - 15

SP - 1

EP - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6941

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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