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

Yohei Kawana, Junta Imai, Yosuke M. Morizawa, Yoko Ikoma, Masato Kohata, Hiroshi Komamura, Toshihiro Sato, Tomohito Izumi, Junpei Yamamoto, Akira Endo, Hiroto Sugawara, Haremaru Kubo, Shinichiro Hosaka, Yuichiro Munakata, Yoichiro Asai, Shinjiro Kodama, Kei Takahashi, Keizo Kaneko, Shojiro Sawada, Tetsuya YamadaAkira Ito, Kuniyasu Niizuma, Teiji Tominaga, Akihiro Yamanaka, Ko Matsui, Hideki Katagiri

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)808-822
Number of pages15
JournalNature Biomedical Engineering
Volume8
Issue number7
DOIs
Publication statusPublished - 2024 Jul

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