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

Nat Commun. 2024 Aug 13;15(1):6941. doi: 10.1038/s41467-024-51076-4.

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.

MeSH terms

  • Animals
  • Glucagon-Like Peptide 1* / metabolism
  • Glucagon-Like Peptide-1 Receptor* / metabolism
  • Glucose / metabolism
  • Insulin / metabolism
  • Insulin Secretion* / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Neurons / metabolism
  • Norepinephrine / metabolism
  • Obesity / metabolism
  • Olfactory Bulb* / drug effects
  • Olfactory Bulb* / metabolism
  • Paraventricular Hypothalamic Nucleus* / metabolism
  • Signal Transduction
  • Sympathetic Nervous System / metabolism

Substances

  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Norepinephrine
  • Glucose
  • Glp1r protein, mouse