A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2024
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| _version_ | 1811140595236732928 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Montaner, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:24:29Z |
| format | Journal article |
| id | oxford-uuid:4d50dc1d-9b19-489d-952b-5ffff08d927b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:24:29Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:4d50dc1d-9b19-489d-952b-5ffff08d927b2024-08-22T20:04:05ZA neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4d50dc1d-9b19-489d-952b-5ffff08d927bEnglishJisc Publications RouterNature Research2024Montaner, MDenom, JSimon, VJiang, WHolt, MKBrierley, DIRouch, CFoppen, EKassis, NJarriault, DKhan, DEygret, LMifsud, FHodson, DJBroichhagen, JVan Oudenhove, LFioramonti, XGault, VCota, DReimann, FGribble, FMMigrenne-Li, STrapp, SGurden, HGlucagon-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. |
| spellingShingle | 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 A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion |
| title | A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion |
| title_full | A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion |
| title_fullStr | A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion |
| title_full_unstemmed | A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion |
| title_short | A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion |
| title_sort | neuronal circuit driven by glp 1 in the olfactory bulb regulates insulin secretion |
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