Three dimensional analysis of beta cell proliferation induced by the vagal signals

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16183
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: Tohoku University
• Principal Investigator: Yamamoto Junpei 東北大学, 医学系研究科, 大学院非常勤講師 (40754924)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 迷走神経 / 膵β細胞 / 糖尿病 / 再生医療 / オプトジェネティクス

Outline of Final Research Achievements

We explored the mechanisms of vagal signal-mediated adaptive β-cell proliferation which is involved in β-cell mass increments during obesity development. First, we generated vagal nerve-visualized mouse and analyzed three-dimensional anatomy of the pancreas, applying a tissue-clearing technology. We found that pancreatic parasympathetic ganglia adjacent to distinct islets seemed to be connected to each other by the same vagal fibers. Next, we developed in vivo optogenetic vagal nerve stimulation methods. Acute vagal activation enhanced glucose stimulated insulin secretion, and chronic vagal activation induced β-cell proliferation and thereby increasing β-cell mass. Moreover, vagal activation prevented elevation of blood glucose in insulin-deficient diabetic model mice. We clarified the importance of vagal nerves in control of both functions and volume of β-cells, and showed the potential of vagal-nerve activations as a novel therapeutic option for insulin-deficient diabetes.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究では、研究代表者の所属研究室が見出した迷走神経シグナルによる細胞増殖・組織適応機構の詳細について、膵内迷走神経系の三次元的構造を解明するとともに、迷走神経の直接的な活性化が膵β細胞増殖を誘導し、糖尿病発症予防効果を示すことを明らかにした。1型糖尿病のみならず2型糖尿病においても膵β細胞量の相対的な減少が病態基盤を形成していることが知られており、本研究により示された迷走神経活性化による膵β細胞増殖機構が、糖尿病の根治療法に応用されることが期待される。