[Tokushima University] Discovery of the 'Insulin Secretion Brake' Regulated by the Autonomic Nervous System: Unraveling a New Inhibitory Mechanism Intensified by Obesity
A joint research group including Tokushima University has discovered that the vagus nerve possesses a 'brake' function that suppresses insulin secretion. They unraveled that this brake function becomes overactive in obesity, leading to decreased insulin secretion.
📋 Article Processing Timeline
- 📰 Published: May 28, 2026 at 11:00
- 🔍 Collected: June 1, 2026 at 01:31 (86h 31m after Published)
- 🤖 AI Analyzed: June 1, 2026 at 23:05 (21h 34m after Collected)
## Overview
A joint research group, including Professor Kei Inoue of the Institute for Enzyme Research at Tokushima University, specially appointed assistant professor Sakumi Hashiuchi and associate professor Yuka Inaba of the Organization for Frontier Research and Development at Kanazawa University, professor Shinya Kuroda of the Graduate School of Science at the University of Tokyo, and visiting researcher Hikaru Sugimoto (then a graduate student at the University of Tokyo Graduate School of Medicine), has revealed that in addition to the conventionally known 'accelerator' function of the vagus nerve, a 'brake' function also exists for regulating insulin secretion.
The brain regulates insulin secretion from the pancreas via the autonomic nervous system. Specifically, the vagus nerve, one of the autonomic nerves, has been known to act as an 'accelerator' that promotes insulin secretion. However, in obesity, this regulation of insulin secretion by the vagus nerve fails, making it impossible to appropriately regulate blood glucose levels. Until now, the mechanism behind why this regulatory abnormality occurs in obesity was not well understood.
In this study, the research group discovered that the vagus nerve also acts as a 'brake' that suppresses insulin secretion. Furthermore, they revealed that this 'brake' function is excessively strengthened in obesity. The newly discovered 'brake action on insulin secretion' is expected to deepen the understanding of the pathology of obesity and type 2 diabetes, and lead to the development of new preventive and therapeutic methods.
The findings were published in the journal *Science Signaling*, published by the American Association for the Advancement of Science (AAAS), on May 26, 2026, at 2:00 PM (EST).
## Research Background
In our bodies, blood glucose levels rise during meals, and insulin secreted from the pancreas keeps blood glucose levels constant. In regulating this insulin secretion, the vagus nerve, an autonomic nerve connecting the brain and pancreas, plays an important role. Specifically, acetylcholine, a representative neurotransmitter of the vagus nerve, is known to promote insulin secretion. Conversely, it has been pointed out that in obesity and type 2 diabetes, such vagal insulin secretion regulation is impaired, leading to glucose intolerance. However, the detailed mechanism of why this regulation is impaired in obesity has remained unclear.
## Summary of Research Results
In this study, the research group revealed that the vagus nerve possesses an 'insulin secretion brake action' mediated by nitric oxide (NO). In addition to the previously known 'insulin secretion promotion action' mediated by acetylcholine, they found that the vagus nerve regulates insulin secretion from both 'accelerator' and 'brake' perspectives.
For this study, they used vagus nerve-activated mice generated using DREADD technology, which allows for drug-dependent control of neural activity. In healthy mice, activating the vagus nerve promoted insulin secretion; however, in obese mice, insulin secretion was conversely suppressed. Therefore, they analyzed the mechanism of vagal insulin secretion suppression observed in obese mice.
Since the vagus nerve is known to promote insulin secretion via acetylcholine, they activated the vagus nerve while inhibiting acetylcholine action with drugs. The insulin secretion promotion observed in healthy mice disappeared, and insulin secretion was conversely suppressed. These results suggested the possibility that a neurotransmitter other than acetylcholine exists in the vagus nerve that suppresses insulin secretion.
In addition to acetylcholine, the vagus nerve transmits information from the brain to the pancreas using NO and neuropeptides as neurotransmitters. Upon analyzing while inhibiting each action, the research group identified that neuronal nitric oxide synthase (nNOS), which synthesizes vagal NO, functions as a brake on insulin secretion.
A joint research group, including Professor Kei Inoue of the Institute for Enzyme Research at Tokushima University, specially appointed assistant professor Sakumi Hashiuchi and associate professor Yuka Inaba of the Organization for Frontier Research and Development at Kanazawa University, professor Shinya Kuroda of the Graduate School of Science at the University of Tokyo, and visiting researcher Hikaru Sugimoto (then a graduate student at the University of Tokyo Graduate School of Medicine), has revealed that in addition to the conventionally known 'accelerator' function of the vagus nerve, a 'brake' function also exists for regulating insulin secretion.
The brain regulates insulin secretion from the pancreas via the autonomic nervous system. Specifically, the vagus nerve, one of the autonomic nerves, has been known to act as an 'accelerator' that promotes insulin secretion. However, in obesity, this regulation of insulin secretion by the vagus nerve fails, making it impossible to appropriately regulate blood glucose levels. Until now, the mechanism behind why this regulatory abnormality occurs in obesity was not well understood.
In this study, the research group discovered that the vagus nerve also acts as a 'brake' that suppresses insulin secretion. Furthermore, they revealed that this 'brake' function is excessively strengthened in obesity. The newly discovered 'brake action on insulin secretion' is expected to deepen the understanding of the pathology of obesity and type 2 diabetes, and lead to the development of new preventive and therapeutic methods.
The findings were published in the journal *Science Signaling*, published by the American Association for the Advancement of Science (AAAS), on May 26, 2026, at 2:00 PM (EST).
## Research Background
In our bodies, blood glucose levels rise during meals, and insulin secreted from the pancreas keeps blood glucose levels constant. In regulating this insulin secretion, the vagus nerve, an autonomic nerve connecting the brain and pancreas, plays an important role. Specifically, acetylcholine, a representative neurotransmitter of the vagus nerve, is known to promote insulin secretion. Conversely, it has been pointed out that in obesity and type 2 diabetes, such vagal insulin secretion regulation is impaired, leading to glucose intolerance. However, the detailed mechanism of why this regulation is impaired in obesity has remained unclear.
## Summary of Research Results
In this study, the research group revealed that the vagus nerve possesses an 'insulin secretion brake action' mediated by nitric oxide (NO). In addition to the previously known 'insulin secretion promotion action' mediated by acetylcholine, they found that the vagus nerve regulates insulin secretion from both 'accelerator' and 'brake' perspectives.
For this study, they used vagus nerve-activated mice generated using DREADD technology, which allows for drug-dependent control of neural activity. In healthy mice, activating the vagus nerve promoted insulin secretion; however, in obese mice, insulin secretion was conversely suppressed. Therefore, they analyzed the mechanism of vagal insulin secretion suppression observed in obese mice.
Since the vagus nerve is known to promote insulin secretion via acetylcholine, they activated the vagus nerve while inhibiting acetylcholine action with drugs. The insulin secretion promotion observed in healthy mice disappeared, and insulin secretion was conversely suppressed. These results suggested the possibility that a neurotransmitter other than acetylcholine exists in the vagus nerve that suppresses insulin secretion.
In addition to acetylcholine, the vagus nerve transmits information from the brain to the pancreas using NO and neuropeptides as neurotransmitters. Upon analyzing while inhibiting each action, the research group identified that neuronal nitric oxide synthase (nNOS), which synthesizes vagal NO, functions as a brake on insulin secretion.
FAQ
迷走神経の新たな発見とは？
迷走神経がインスリン分泌を促進する「アクセル」機能だけでなく、インスリン分泌を抑制する「ブレーキ」機能も持っていることを明らかにしました。
肥満とインスリン分泌低下の関連は？
肥満状態では、迷走神経の「ブレーキ」機能が過剰に働くため、インスリンの分泌が抑制され、血糖値調節が困難になることが判明しました。
今回の研究成果はいつ発表されましたか？
2026年5月26日午後2時（米国東部標準時）に科学誌『Science Signaling』に掲載されました。
どのような手法で研究が行われましたか？
薬剤依存的に神経活動を制御できるDREADD技術を用いて作成した迷走神経活性化マウスを使用し、解析を行いました。
今後の展望は？
今回発見したインスリン分泌の「ブレーキ」作用を標的とすることで、肥満や2型糖尿病の新たな予防法や治療法の開発が期待されています。