Development of new therapeutic agents for diabetic complications including periodontal disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10079
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Nihon University
• Principal Investigator: OHASHI Akiko 日本大学, 歯学部, 助教 (00571019)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: テトラヒドロビオプテリン / 血管障害 / 酸化ストレス

Outline of Final Research Achievements

In studies using model animals, supplementation with tetrahydrobiopterin (BH4), which regulates the eNOS response, is effective for angiopathy caused by eNOS dysfunction.However, sufficient results have not been obtained in clinical trials.We noted that the causes were the oxidation of BH4 and the inefficiency of BH4 replenishment.In this study, we showed that BH4 oxidation occurs enzymatically in cells and tissues rather than autoxidation, and that NADPH oxidase is involved in this BH4 oxidation. On the other hand, it was shown that the activity of the transporter responsible for BH4 transport, which determines the BH4 replenishment efficiency, is affected by osmotic pressure.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

糖尿病の主な合併症は細小血管症 (腎症，網膜症，神経障害)，大血管症(脳梗塞，心筋梗塞)である。これら血管症に次ぐ合併症として歯周病が注目されている。歯周病と糖尿病は相互に負の影響を与えるため，糖尿病患者において有意に悪化するだけでなく，歯周病が糖尿病の合併症(腎症，心疾患)を悪化させる。本研究成果は，BH4の酸化とBH4補充効率を改善する一助であり，歯周病ならびに糖尿病の合併症の有効な治療によって，多くの患者の生活の質の維持と健康寿命の延長への貢献が期待できる。