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

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.

SUBMITTER: Kawana Y

PROVIDER: S-EPMC11310082 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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

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

Nature biomedical engineering 20231109 7

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 ...[more]

PMID: 37945752

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Project description:UnlabelledLow-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS) resulting in endotoxemia could be a candidate. Here we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin/delta0-15glucose) from 13.73 to 22.40 pmol/mmol (P < 0.001). This aberration in insulin and glucose homeostasis was normalized by resveratrol.In conclusionLow-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin secretion.

Dataset Information

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

Publications

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

Similar Datasets

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