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A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion.
- Source :
-
Nature communications [Nat Commun] 2024 Aug 13; Vol. 15 (1), pp. 6941. Date of Electronic Publication: 2024 Aug 13. - Publication Year :
- 2024
-
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 α <subscript>2</subscript> -adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABA <subscript>A</subscript> 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Male
Mice
Insulin metabolism
Obesity metabolism
Sympathetic Nervous System metabolism
Neurons metabolism
Signal Transduction
Norepinephrine metabolism
Glucose metabolism
Glucagon-Like Peptide 1 metabolism
Olfactory Bulb metabolism
Olfactory Bulb drug effects
Insulin Secretion drug effects
Glucagon-Like Peptide-1 Receptor metabolism
Paraventricular Hypothalamic Nucleus metabolism
Mice, Inbred C57BL
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39138162
- Full Text :
- https://doi.org/10.1038/s41467-024-51076-4