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Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and β cell proliferation

2023/11/09 by Yohei Kawana, Junta Imai, Yosuke M. Morizawa +23 · 1 voice · 2 citations
Medicine · Neuroscience · #Pancreatic function and diabetes #Photoreceptor and optogenetics research #Vagus Nerve Stimulation Research

paper · doi:10.1038/s41551-023-01113-2

openalex publication_date 2023/11/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23

Abstract

The enhancement of insulin secretion and of the proliferation of pancreatic β cells are promising therapeutic options for diabetes. Signals from the vagal nerve regulate both processes, yet the effectiveness of stimulating the nerve is unclear, owing to a lack of techniques for doing it so selectively and prolongedly. Here we report two optogenetic methods for vagal-nerve stimulation that led to enhanced glucose-stimulated insulin secretion and to β cell proliferation in mice expressing choline acetyltransferase-channelrhodopsin 2. One method involves subdiaphragmatic implantation of an optical fibre for the photostimulation of cholinergic neurons expressing a blue-light-sensitive opsin. The other method, which suppressed streptozotocin-induced hyperglycaemia in the mice, involves the selective activation of vagal fibres by placing blue-light-emitting lanthanide microparticles in the pancreatic ducts of opsin-expressing mice, followed by near-infrared illumination. The two methods show that signals from the vagal nerve, especially from nerve fibres innervating the pancreas, are sufficient to regulate insulin secretion and β cell proliferation.

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