Regulation of renal renin-angiotensin system and renal gluconeogenesis as a diabetic therapy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09285
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Dokkyo Medical University (2017); The University of Tokyo (2015-2016)
• Principal Investigator: Tojo Akihiro 獨協医科大学, 医学部, 准教授 (50292917)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 糖尿病 / 腎糖新生 / 尿細管 / アンジオテンシノーゲン / エンドサイトーシス / プロトンポンプ / アンモニア産生

Outline of Final Research Achievements

The kidney plays an important role in gluconeogenesis, and in the starvation condition, amount of renal gluconeogenesis increases as same as that in the liver. H+-ATPase has important roles in the activation of cytoplasmic enzymes, endocytosis and membrane recycling of channels and receptors by acidification of vesicles. In renal gluconeogenesis, glutamine converted to alpha-ketoglutarate with 2 molecules of ammonium in mitochondria, then alpha-ketoglutarate was used for gluconeogenesis. Proteins related to ammoniagenesis and gluconeogenesis were increased in the kidney of diabetes, and bafilomycin treatment inhibited renal gluconeogenesis and lowered plasma glucose to the control levels. The regulation of renal gluconeogenesis by H+-ATPase inhibitor could be a new therapeutic target of diabetes mellitus.

Free Research Field

腎臓内科学・高血圧・腎病理学