The mechanism of the effect of Alzheimer's disease on the systemic glucose metabolism

• Project/Area Number: 18K16190
• 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: Tohoku University
• Principal Investigator: Asai Yoichiro 東北大学, 大学病院, 助教 (50754925)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 糖尿病 / アルツハイマー型認知症 / インスリン抵抗性 / 認知症 / 臓器連関

Outline of Final Research Achievements

The effects of sporadic Alzheimer's disease on systemic glucose metabolism were investigated. The intra-cerebroventricular injection of streptozotocin(STZ) caused wild type mice cognitive dysfunction. The inflammation with the increase of microglia was observed in the areas of hippocampus and entorhinal cortex of STZ-icv mice. Furthermore, STZ-icv mice exhibited hyper-insulinemia and insulin resistance. The expression levels of insulin signal-related genes were different between the liver and the skeletal muscles.
These results suggest the possibility that Alzheimer's disease itself may bring systemic insulin resistance.

Academic Significance and Societal Importance of the Research Achievements

これまで、糖尿病やインスリン抵抗性がアルツハイマー型認知症の発症を促進する機序について数多くの研究が報告されている一方で、アルツハイマー型認知症自体が糖代謝に与える影響についての報告はほとんどない。本研究は、アルツハイマー型認知症が糖尿病・インスリン抵抗性を悪化させ、さらに認知症を促進させるという悪循環を来しうる可能性を示唆しており、認知症と糖代謝異常の進行を予防する為の基盤の知見となる事が考えられる。

Research Products

• [Journal Article] Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report (2019)
  • Author(s): Kaneko K, Satake C, Izumi T, Tanaka M, Yamamoto J, Asai Y, Sawada S, Imai J, Yamada T, Katagiri H.
  • Journal Title: BMC Endocr Disord. Volume: 19 Issue: 1 Pages: 5-5
  • DOI: 10.1186/s12902-018-0326-3
  • Peer Reviewed / Open Access
• [Journal Article] Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation. (2018)
  • Author(s): Izumi T, Imai J, Yamamoto J, Kawana Y, Endo A, Sugawara H, Kohata M, Asai Y, Takahashi K, Kodama S, Kaneko K, Gao J, Uno K, Sawada S, Kalinichenko VV, Ishigaki Y, Yamada T, Katagiri H.
  • Journal Title: Nat Commun. Volume: 9 Issue: 1 Pages: 5300-5300
  • DOI: 10.1038/s41467-018-07747-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Book] 決定版 阻害剤・活性化剤ハンドブック (2019)
  • Author(s): 浅井洋一郎, 片桐秀樹
  • Total Pages: 13
  • Publisher: 羊土社