NYMC Faculty Publications

Vagal Sensory Neuron-Derived FGF3 Controls Insulin Secretion

Author Type(s)

Faculty

DOI

10.1016/j.devcel.2024.09.016

Journal Title

Developmental Cell

First Page

51

Last Page

61.e4

Document Type

Article

Publication Date

1-6-2025

Department

Cell Biology and Anatomy

Keywords

autonomic nervous system, FGF3, glucose homeostasis, insulin resistance, insulin secretion, islet pancreatic β cells, RNA sequencing, sensory neurons, vagal nerve stimulation, vagus nerve

Disciplines

Medicine and Health Sciences

Abstract

Vagal nerve stimulation has emerged as a promising modality for treating a wide range of chronic conditions, including metabolic disorders. However, the cellular and molecular pathways driving these clinical benefits remain largely obscure. Here, we demonstrate that fibroblast growth factor 3 (Fgf3) mRNA is upregulated in the mouse vagal ganglia under acute metabolic stress. Systemic and vagal sensory overexpression of Fgf3 enhanced glucose-stimulated insulin secretion (GSIS), improved glucose excursion, and increased energy expenditure and physical activity. Fgf3-elicited insulinotropic and glucose-lowering responses were recapitulated when overexpression of Fgf3 was restricted to the pancreas-projecting vagal sensory neurons. Genetic ablation of Fgf3 in pancreatic vagal afferents exacerbated high-fat diet-induced glucose intolerance and blunted GSIS. Finally, electrostimulation of the vagal afferents enhanced GSIS and glucose clearance independently of efferent outputs. Collectively, we demonstrate a direct role for the vagal afferent signaling in GSIS and identify Fgf3 as a vagal sensory-derived metabolic factor that controls pancreatic β-cell activity.

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