Regulation of nicotinamide metabolism by glucagon

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H03176
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Nagoya University
• Principal Investigator: Hayashi Yoshitaka 名古屋大学, 環境医学研究所, 教授 (80420363)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: グルカゴン / 糖尿病 / ニコチンアミド / サーチュイン / アミノ酸 / 糖代謝 / エネルギー代謝

Outline of Final Research Achievements

Expression levels of nicotinamide N-methyltransferase (NNMT) mRNA are diminished in the liver of glucagon gene knock-out mouse (GCGKO). As amino acid metabolism is largely altered in GCGKO, we explored possible involvement of NNMT in regulation of amino acid metabolism, as well as glucose metabolism.
To this end, we generated mouse models which lack NNMT ubiquitously or in a liver-specific manner (NNMTKO and NNMTLKO, respectively). We also crossed these models with GCGKO to produce double knockout models for NNMT and GCGKO (NNMT/GCG DKO).
NNMTKO, NNMTLKO and NNMT/GCGDKO were born according to expected ratio, indicating that NNMT is not absolutely required for development and survival. No significant difference in the expression levels of genes involved in metabolism of amino acids and glucose was observed between the control and KO mice. Therefore, NNMT plays relatively minor role in the regulation of amino acid metabolism, at least under normal or disease-free conditions.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

NADは老化や寿命の制御に重要な役割を果たすサーチュインの作用において不可欠の役割を果たす物質である。NNMT(ニコチンアミドNメチル基転移酵素)はNADの構成要素のニコチンアミドを働かなくする働きを持つ。我々は血糖上昇ホルモンであるグルカゴンを欠損するモデル動物においてNNMT遺伝子の働きが非常に弱くなっていることを発見・報告してきた。
そこでNNMTの生体における役割を明らかにするためにNNMT遺伝子の欠損モデル動物を作成した。解析の結果、同モデルの発達・生存・血糖値などには異常を認めなかったが、この結果はニコチンアミドを通常よりも多く摂取しても安全であることを示唆していると考えられる。