The role of hepatic gluconeogenesis in systemic metabolism

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tohoku University
• Principal Investigator: Kaneko Keizo 東北大学, 大学病院, 講師 (60546141)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖新生

Outline of Final Research Achievements

Gluconeogenesis is performed by the liver and kidneys. Hepatic gluconeogenesis is considered to be a main contributor to systemic glucose production. The gluconeogenic pathway initiated from glycerol, using glycerol kinase (Gyk), is reported to be important during fasting state and in diabetes. Our research is aimed at investigating how the Gyk gluconeogenc pathway in the liver is involved in the systemic glucose homeostasis, using the liver-specific Gyk knockout (KO) mouse. The results so far showed no strong phenotypes of glucose homeostasis in the liver-specific GykKO mouse (L-GykKO) during fasting and obesity development. We thus created the mice with Gyk deletion both in the liver and kidneys (LK-GykKO). Very little glucose was produced from glycerol in LK-GykKO, compared to L-GykKO. This result indicated that the intervention of Gyk pathways in both liver and kidneys is important to clarify the role of Gyk pathway in the systemic glucose homeostasis.

Free Research Field

糖代謝

Academic Significance and Societal Importance of the Research Achievements

研究開始初期においては、糖新生の中で重要な経路の1つのGyk経路の全身代謝における役割を肝臓へのアプローチで解明することを目指していた。しかし、研究をすすめるうちに肝以外の腎の糖新生へのアプローチも必要であることが分かり、このことは1つの成果であると考えている。今回の研究データの上に肝腎2つの糖新生臓器のGyk経路への介入実験を積み重ねていくことで、糖新生Gyk経路による個体レベルでの代謝制御を探究し、血糖恒常性の維持の解明や肥満糖尿病への新規アプローチへとつなげていく予定である。