Regulation of nicotinamide metabolism by glucagon
| Project/Area Number |
18H03176
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| 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 / 代謝制御 / 肝臓 / 門脈-中心静脈領域特異性 / 膵島内分泌腫瘍 / 腫瘍微小環境 / アミノ酸代謝 / カロリー制限 / ニコチンアミドNメチルトランスフェラーゼ / 生体恒常性 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(46 results)
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[Journal Article] Deficiency of glucagon gene-derived peptides induces peripheral polyneuropathy in mice.2020
Author(s)
Mikio Motegi, Tatsuhito Himeno, Hiromi Nakai-Shimoda, Rieko Inoue, Norio Ozeki, Keiko Naruse, Yusuke Seino, Yoshitaka Hayashi, Jiro Nakamura, Hideki Kamiya, et al.
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 532
Issue: 1
Pages: 47-53
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion2019
Author(s)
Liu Y, Harashima SI, Wang Y, Suzuki K, Tokumoto S, Usui R, Tatsuoka H, Tanaka D, Yabe D, Harada N, Hayashi Y, Inagaki N.
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Journal Title
FASEB J.
Volume: 33
Issue: 5
Pages: 6239-6253
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functional adenosine triphosphate-sensitive potassium channel is required in high-carbohydrate diet-induced increase in β-cell mass.2019
Author(s)
Murase M, Seino Y, Maekawa R, Iida A, Hosokawa K, Hayami T, Tsunekawa S, Hamada Y, Yokoi N, Seino S, Hayashi Y, Arima H
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Journal Title
J Diabetes Investig
Volume: 10（2）
Issue: 2
Pages: 238-250
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Glucose-dependent insulinotropic polypeptide is required for moderate high fat diet, but not high carbohydrate diet-induced weight gain.2018
Author(s)
Maekawa R, Ogata H, Murase M, Harada N, Suzuki K, Joo E, Sankoda A, Iida A, Izumoto T, Tsunekawa S, Hamada Y, Oiso Y, Inagaki N, Arima H, Hayashi Y, Seino Y.
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Journal Title
Am J Physiol Endocrinol Metab.
Volume: 6
Issue: 6
Pages: 111-112
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] No significant change of glucagon level by empagliflozin in diabetic mice.2019
Author(s)
Shimoda H, Seino Y, Himeno T, Inoue R, Motegi M, Hayami T, Asano E, Asano S, Kato M, Yamada Y, Miura-Yura E, Kondo M,Tsunekawa S, Kato Y, Kato K, Hayashi Y, Nakamura J, Kamiya H
Organizer
79th Scientific Sessions of the American-Diabetes-Association
Related Report
Int'l Joint Research
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[Presentation] マウス末梢神経系におけるグルカゴン遺伝子由来ペプチドの生理的役割の解明2019
Author(s)
茂木 幹雄, 姫野 龍仁, 神谷 英紀, 下田 博美, 三浦 絵美梨, 井上 利恵子, 尾関 教生, 近藤 正樹, 恒川 新, 加藤 義郎, 林 良敬, 中村 二郎
Organizer
第62回日本糖尿病学会年次学術集会
Related Report
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[Presentation] SGLT2阻害薬がグルカゴン濃度におよぼす影響の検討 グルカゴン遺伝子欠損マウスを用いた比較2019
Author(s)
下田 博美, 清野 祐介, 姫野 龍仁, 浅野 紗恵子, 茂木 幹雄, Mohiuddin Sarif, 近藤 正樹, 恒川 新, 加藤 義郎, 神谷 英紀, 林 良敬, 中村 二郎
Organizer
第62回日本糖尿病学会年次学術集会
Related Report
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