Investigation of the regulatory mechanism of hepatic glucose response

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19545
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Inoue Hiroshi 金沢大学, 新学術創成研究機構, 教授 (50397832)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 肝臓 / 糖取り込み

Outline of Final Research Achievements

The liver takes up glucose and triggers glucose responses, including not only hepatic metabolism but also transcriptional regulation and inter-organ crosstalk with other organs. In overnutrition and obesity, hepatic glucose response is impaired, which contributes to the pathogenesis of glucose intolerance, insulin resistance, and fatty liver. This study aimed to elucidate the role of glucokinase regulatory protein (GKRP) in the control mechanism of hepatic glucose response. GKRP undergoes increased acetylation at lysine 126 (K126) due to overnutrition and obesity. Although K126R mutant knock-in mice of GKRP did not show significant changes in hepatic glucose metabolism, transcriptome analysis revealed changes in gene expression. This suggests that GKRP may be a novel glucose response control molecule.

Free Research Field

健康科学および栄養代謝内分泌学

Academic Significance and Societal Importance of the Research Achievements

肝グルコース応答障害は、耐糖能障害からインスリン抵抗性・脂肪肝などの様々な生活習慣病の病因となる。肝グルコース応答の制御分子としてGckが知られてきたが、Gckを標的とした生活習慣病治療薬の開発は十分な成果が得られていない。本研究において、新規な肝グルコース応答のメカニズム分子候補としてGKRPを見出すことは、生活習慣病の新規治療標的の解明に繋がる。さらに、生活習慣病の発症と増悪において、肝グルコース応答とその障害が果たす役割の解明へと繋がる。