Evaluation of bioactivity of glucagon and glucagon-related peptides using a novel bioassay method

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17488
• 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: Shiga University of Medical Science
• Principal Investigator: YANAGIMACHI Tsuyoshi 滋賀医科大学, 医学部, 助教 (20596275)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: グルカゴン / GLP-1

Outline of Final Research Achievements

Oxyntomodulin (OXM) is a gastrointestinal hormone with high amino acid sequence homology to glucagon, and we observed that glucagon was inactivated by DPP-4 and neprilysin (NEP), but OXM, unlike glucagon, was not inactivated by NEP. The effect of NEP on glucagon and OXM was examined using LC-MS/MS. 3 peaks were observed for glucagon in the presence of NEP, but only one large peak was observed for OXM, confirming the formation of OXM(1-35) from OXM(1-37). OXM(1-35) lowered blood glucose levels and promoted insulin secretions as well as OXM(1-37), suggesting that OXM may be more effective than conventional diabetes treatment because it is less likely to be inactivated.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

オキシントモジュリン（OXM）は37個のアミノ酸から構成され、グルカゴンと非常に高い相同性を有したホルモンで、血糖値を上げるグルカゴンと血糖値を下げるGLP-1の二つのホルモンの受容体活性を有している。OXMは血糖降下作用を示すことが報告されているが、詳細な検討は非常に少ない。今回我々は分解酵素の一つであるNeprilycinによって、OXMは37個（OXM（1－37））から35個（OXM（1-35）)のアミノ酸配列に変化し、この分解産物であるOXM（1-35）も血糖降下作用を有することを明らかにした。OXMは他のホルモンより不活化を受けにくく、従来の糖尿病治療薬より有効な可能性が示唆された。