Elucidation of the role of short-form GIP in glucose metabolism and its application to drug discovery

2024 Fiscal Year Final Research Report

• Project/Area Number: 19K17996
• 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: Kanazawa Medical University (2022-2024); Asahikawa Medical College (2019-2021)
• Principal Investigator: TAKEDA Yasutaka 金沢医科大学, 医学部, 講師 (90431402)
• Project Period (FY): 2019-04-01 – 2025-03-31
• Keywords: GIP(1-30) / インクレチン / 糖代謝

Outline of Final Research Achievements

This study was conducted to clarify the secretion and clinical significance of GIP(1-30). GIP(1-30) secretion in a 75g OGTT tended to be lower in prediabetic and type 2 diabetic patients compared to subjects with normal glucose tolerance, and its AUC correlated with the insulinogenic index during OGTT. Although the blood GIP(1-30) concentration in patients after total pancreatectomy was below the lower limit of quantification, some patients were quantifiable. In immunohistochemistry using an antibody against the C-terminus of GIP(1-30)(GIP(24-30)), GIP(24-30) staining was observed in human pancreatic alpha cells, which was lower in type 2 diabetic patients compared to nondiabetic patients. GIP(24-30) staining was also observed in the human small intestine, suggesting that GIP(1-30) may originate from the pancreas and small intestine.

Free Research Field

代謝・内分泌

Academic Significance and Societal Importance of the Research Achievements

本研究では、(1)生体においてGIP(1-30)がインスリン分泌と関連すること、(2)GIP(1-30)が主に膵島由来であるほか小腸に由来したGIP(1-30)が存在すること、(3)2型糖尿病ではGIP(1-30)の分泌が低下している可能性があることを見出した。これらの知見は、糖代謝におけるGIP(1-30)の役割の一端を示すに留まらず、糖代謝異常の病態・病因を解明する上で、新たな知見となる可能性がある。本研究課題では、GIP(1-30)の分泌調節機構も検証する予定であったが、COVID-19感染症の流行や能登半島地震の影響もあり、当初の計画通りに遂行できなかった。今後改めて取り組みたい。