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 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 Gault, Daniela Cota, Frank ReimannFiona M Gribble, Stephanie Migrenne-Li, Stefan Trapp, Hirac Gurden, Christophe Magnan

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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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.

Originele taal-2	Engels
Pagina's (van-tot)	6941
Tijdschrift	Nature Communications
Volume	15
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-024-51076-4
Status	Gepubliceerd - aug. 2024

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10.1038/s41467-024-51076-4

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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., Van Oudenhove, L., Fioramonti, X., Gault, V., Cota, D., ... Magnan, C. (2024). A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion. Nature Communications, 15(1), 6941. 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 = "Animals, Glucagon-Like Peptide 1/metabolism, Male, Olfactory Bulb/metabolism, Insulin Secretion/drug effects, Glucagon-Like Peptide-1 Receptor/metabolism, Mice, Paraventricular Hypothalamic Nucleus/metabolism, Mice, Inbred C57BL, Insulin/metabolism, Obesity/metabolism, Sympathetic Nervous System/metabolism, Neurons/metabolism, Signal Transduction, Norepinephrine/metabolism, Glucose/metabolism",

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 {Van Oudenhove}, Lukas and Xavier Fioramonti and Victor Gault and Daniela Cota and Frank Reimann and Gribble, {Fiona M} and Stephanie Migrenne-Li and Stefan Trapp and Hirac Gurden and Christophe Magnan",

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

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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, Van Oudenhove, L, Fioramonti, X, Gault, V, 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, nr. 1, blz. 6941. https://doi.org/10.1038/s41467-024-51076-4

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T1 - A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

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 - Van Oudenhove, Lukas

AU - Fioramonti, Xavier

AU - Gault, Victor

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

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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 - Animals

KW - Glucagon-Like Peptide 1/metabolism

KW - Male

KW - Olfactory Bulb/metabolism

KW - Insulin Secretion/drug effects

KW - Glucagon-Like Peptide-1 Receptor/metabolism

KW - Mice

KW - Paraventricular Hypothalamic Nucleus/metabolism

KW - Mice, Inbred C57BL

KW - Insulin/metabolism

KW - Obesity/metabolism

KW - Sympathetic Nervous System/metabolism

KW - Neurons/metabolism

KW - Signal Transduction

KW - Norepinephrine/metabolism

KW - Glucose/metabolism

U2 - 10.1038/s41467-024-51076-4

DO - 10.1038/s41467-024-51076-4

M3 - Article

C2 - 39138162

SN - 2041-1723

VL - 15

SP - 6941

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -