The Impact of Amino Acid Imbalance and Abnormal Sphingolipid Accumulation on Diabetic Polyneuropathy

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20900
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Aichi Medical University
• Principal Investigator: Nakai-Shimoda Hiromi 愛知医科大学, 医学部, 助教 (40740931)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 糖尿病性神経障害

Outline of Final Research Achievements

To elucidate the pathology of diabetic polyneuropathy (DPN), we focused on the accumulation of abnormal sphingolipids based on amino acid imbalance. Given that L-serine, a component molecule of sphingolipids, decreases in diabetic patients while abnormal sphingolipids in the blood increase, we hypothesized that changes in amino acid concentrations trigger abnormal sphingolipid accumulation in tissues. We investigated whether abnormal sphingolipids are involved in the pathology of DPN. As a result, we confirmed the expression of amino acid transporters in the peripheral nervous system of DPN mice. Additionally, we confirmed a decrease in the expression of Sptlc1, a key factor involved in sphingolipid synthesis in the endoplasmic reticulum. We plan to further analyze these data and continue to elucidate the pathology of DPN.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

近年は盛んに酸化ストレスがDPNの主要な病態であるとの仮説が検証されてきたものの臨床研究では仮説を裏切る結果が得られている。そのため、引き続き現在も国内外の研究者の間では、新規病態の解明が切望されている。
今回注目した異常スフィンゴ脂質とDPNの関係については、病理学的変化および分子生物学的メカニズムは十分に評価されていない。本研究の結果、新たな治療ターゲットの確立に繋がることが期待できる。