Role of ectopic olfactory receptor system in pancreatic beta cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17997
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tohoku University
• Principal Investigator: Munakata Yuichiro 東北大学, 大学病院, 助教 (60747070)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: インスリン分泌 / 糖尿病 / 嗅覚受容体 / 膵β細胞

Outline of Final Research Achievements

In this project, we searched for candidate ligands of olfactory receptor (OR) expressed in pancreatic beta cells and examined whether OR-mediated glucose-stimulated insulin secretion (GSIS) enhancement was potentiated by incretin signaling.
Our present study raised the possibility that amyl hexanoate (AH) and allyl phenylacetate (AP) were new ligands of OLFR15 expressed in pancreatic beta cells. Furthermore, we elucidated that GSIS from pancreatic beta cells was significantly enhanced by the combination of AH and GLP1 compared with AH or GLP1.
These results suggest that the OR system in pancreatic beta cells may constitute a potential therapeutic target for type 2 diabetes by enhancing insulin secretion.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

嗅覚受容体を介したインスリン分泌促進機構は、既存の糖尿病薬と別経路を用い、活性化により高血糖時のみインスリン分泌を増強する。そのため、本研究で得られた結果と併せて、低血糖を起こさずGSISを増強することで糖尿病を治療する新規薬剤の開発につながる可能性が示唆された。インスリン分泌不全が2型糖尿病の成因として重要であることが知られている我が国においては特に有益な治療選択肢を増やすことにつながり得る成果と考えられた。