Importance of primary cillia Hedgehog signaling in glucose metabolism of diabetic beta cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08537
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Ritsumeikan University
• Principal Investigator: Mukai Eri 立命館大学, 生命科学部, 教授 (60362539)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: インスリン分泌 / 糖尿病 / 一次繊毛 / ヘッジホッグシグナル / β細胞

Outline of Final Research Achievements

The purpose of this study is to clarify the involvement of Hh signaling in glucose metabolism abnormalities in diabetes mellitus and its molecular mechanism. Glucose-stimulated insulin secretion was significantly enhanced only by cyclopamine, which is a partial agoint among Hh signaling stimulants. Furthermore, it was shown that enhanced insulin secretion by cyclopamine is attributed to increasing mitochondrial ATP production. It was also suggested that Smoothened, Gpr161, and unknown canonical signaling factors independent of AMPK may be involved in insulin secretion.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

Hhシグナルはこれまで他の臓器と同様に膵臓の発生・分化に関与することは示されているが、成熟膵β細胞における機能やグルコース代謝への関与は検討されていない。それどころか、β細胞における一次繊毛シグナルと糖代謝との関係を明らかにする検討はなされておらず、これまでにない発想であることから学術的独自性が高い。この糖尿病における代謝のスイッチングメカニズムが明らかにされれば、糖尿病の膵β細胞障害の理解において画期的な研究発展となり得る。