Research for intracellular metabolism in pancreatic beta-cell under diabetic condition

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17503
• 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: Hokkaido University
• Principal Investigator: NOMOTO Hiroshi 北海道大学, 大学病院, 助教 (50862330)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖尿病 / 膵β細胞 / 細胞内代謝

Outline of Final Research Achievements

We focused on the intracellular metabolic changes in pancreatic β-cells in which energy metabolism shifts from oxidative phosphorylation to glycolysis via PFKFB3 expression in diabetic conditions.
In this application, we clarified that PFKFB3 is expressed at various levels in the pancreatic β-cells of Japanese subjects with type 2 diabetes, and showed its relationship closely correlated with patients’ background. Furthermore, using obese diabetic model mice and pancreatic β-cell strains, we demonstrated that this intracellular metabolic change is reversible and that intervention on diabetic condition can affect different outcome on intracellular metabolisms.

Free Research Field

糖尿病・内分泌

Academic Significance and Societal Importance of the Research Achievements

本申請課題により、日本人の2型糖尿病患者において膵β細胞の細胞内代謝異常と密接に関連するPFKFB3の発現が亢進していることが明らかとなった。患者背景や背景膵の組織像がこのPFKFB3の発現に関連し、さらに種々の糖尿病病態への介入が更新したPFKFB3の発現を改善させることが明確となった。今後は糖尿病病態下で発現が増強しているPFKFB3の意義の解明や、直接の治療標的となりうるかの検討を行うことが必要である。