A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion.
Nat Commun
; 15(1): 6941, 2024 Aug 13.
Article
in En
| MEDLINE
| ID: mdl-39138162
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Olfactory Bulb
/
Paraventricular Hypothalamic Nucleus
/
Glucagon-Like Peptide 1
/
Glucagon-Like Peptide-1 Receptor
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Insulin Secretion
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Mice, Inbred C57BL
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country: