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Molecular mechanisms of disorder of pancreatic beta cells induced by excess selenoprotein P

Research Project

Project/Area Number 17H03821
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionTohoku University

Principal Investigator

Saito Yoshiro  東北大学, 薬学研究科, 教授 (70357060)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywordsセレン / 膵β細胞 / インスリン分泌 / 小胞体ストレス / 膵肝代謝制御 / フェロトーシス / アポトーシス / リポプロテイン受容体 / インスリン / 親電子物質 / 発現制御 / 2型糖尿病 / セレノプロテイン / 糖尿病 / 中和抗体 / 疾患モデルマウス / 栄養学 / 食品 / 細胞・組織
Outline of Final Research Achievements

Selenoprotein P (SeP), a plasma protein containing essential trace element selenium, functions as a transporter of selenium, delivering selenium to the cells. We found the increase of SeP levels in type 2 diabetes patients and have reported that increased SeP (excess SeP) worsen glucose metabolism via the increase of insulin resistance in the skeletal muscle and liver. In the present study, we found that excess SeP is incorporated into the pancreatic beta cells via SeP receptors and decreases insulin secretion via ER stress. Furthermore, we found the physiological role of SeP expression in the pancreatic beta cells and stated the novel metabolism regulation between the pancreas and liver via insulin and SeP.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、膵β細胞の機能を制御する新たな機構が明らかとなり、膵β細胞を保護し、2型糖尿病を治療する新たな戦略が見いだされた。さらに、膵β細胞におけるSeP発現の意義、およびインスリンを介したSeP発現制御機構が見いだされ、分泌因子を介した密接な膵肝代謝制御機構が明らかとなった。本研究成果をさらに進展することで、未だ開発されていない膵機能保護薬の開発が実現できると確信する。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (48 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 18 results,  Open Access: 16 results) Presentation (24 results) (of which Int'l Joint Research: 7 results,  Invited: 22 results) Book (2 results) Remarks (2 results)

  • [Int'l Joint Research] National Institute of Oncology/Dept. of Mol Immunol Toxicol(ハンガリー)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Panum Institute University of Copenhagen(デンマーク)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Selenoprotein P; P for Plasma, Prognosis, Prophylaxis, and More2020

    • Author(s)
      Tsutsumi Ryouhei、Saito Yoshiro
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 3 Pages: 366-374

    • DOI

      10.1248/bpb.b19-00837

    • NAID

      130007804438

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-03-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selenoprotein P as an <i>in vivo</i> redox regulator: disorders related to its deficiency and excess2020

    • Author(s)
      Saito Yoshiro
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 66 Issue: 1 Pages: 1-7

    • DOI

      10.3164/jcbn.19-31

    • NAID

      130007779262

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating Concentrations of Insulin Resistance-Associated Hepatokines, Selenoprotein P and Leukocyte Cell-Derived Chemotaxin 2, during an Oral Glucose Tolerance Test in Humans2019

    • Author(s)
      Mohri K, Misu H, Takayama H, Ishii KA, Kikuchi A, Lan F, Enyama Y, Takeshita Y, Saito Y, Kaneko S,Takamura T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 3 Pages: 373-378

    • DOI

      10.1248/bpb.b18-00549

    • NAID

      130007607371

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-03-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diagnostic and Prognostic Significance of Serum Levels of SeP (Selenoprotein P) in Patients with Pulmonary Hypertension2019

    • Author(s)
      Nobuhiro Kikuchi, Kimio Satoh, Taijyu Satoh, Nobuhiro Yaoita, Mohammad Abdul Hai Siddique, Junichi Omura, Ryo Kurosawa, Masamichi Nogi, Shinichiro Sunamura, Satoshi Miyata, Hirofumi Misu, Yoshiro Saito, Hiroaki Shimokawa
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 39 Issue: 12 Pages: 2553

    • DOI

      10.1161/atvbaha.119.313267

    • URL

      https://localhost/en/publications/be0d8f72-5974-4474-907e-2c1b5325427e

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selenoprotein P as a significant regulator of pancreatic β cell function2019

    • Author(s)
      Saito Yoshiro
    • Journal Title

      The Journal of Biochemistry

      Volume: 167 Pages: 119-124

    • DOI

      10.1093/jb/mvz061

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Response by Kikuchi et al regarding article, "selenoprotein P promotes the development of pulmonary arterial hypertension: a possible novel therapeutic target"2019

    • Author(s)
      Kikuchi N, Satoh K, Saito Y, Shimokawa H.
    • Journal Title

      Circulation

      Volume: 139 Issue: 5 Pages: 724-725

    • DOI

      10.1161/circulationaha.118.038479

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrogen Peroxide-Reducing Factor Released by PC12D Cells Increases Cell Tolerance against Oxidative Stress2018

    • Author(s)
      Asami Muraishi, Emi Haneta, Yoshiro Saito, Yutaka Hitomi, Mamoru Sano, Noriko Noguchi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 5 Pages: 777-785

    • DOI

      10.1248/bpb.b18-00016

    • NAID

      130006730719

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-05-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Human Selenoprotein P Determinants in Serum between Our Original Methods and Commercially Available Kits2018

    • Author(s)
      Saito Yoshiro、Misu Hirofumi、Takayama Hiroaki、Takashima Shin-ichiro、Usui Soichiro、Takamura Masayuki、Kaneko Shuichi、Takamura Toshinari、Noguchi Noriko
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 5 Pages: 828-832

    • DOI

      10.1248/bpb.b18-00046

    • NAID

      130006730702

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-05-01
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population.2018

    • Author(s)
      Oo SM, Misu H, Saito Y, Tanaka M, Kato S, Kita Y, Takayama H, Takeshita Y, Kanamori T, Nagano T, Nakagen M, Urabe T, Matsuyama N, Kaneko S, Takamura T.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 16727-16727

    • DOI

      10.1038/s41598-018-35067-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distribution of oxidized DJ-1 in Parkinson’s disease-related sites in the brain and in the peripheral tissues: effects of aging and a neurotoxin2018

    • Author(s)
      Mita Yuichiro、Kataoka Yuto、Saito Yoshiro、Kashi Takuma、Hayashi Kojiro、Iwasaki Asa、Imanishi Takanori、Miyasaka Tomohiro、Noguchi Noriko
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 12056-12056

    • DOI

      10.1038/s41598-018-30561-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tocopherol suppresses 24(S)-hydroxycholesterol-induced cell death via inhibition of CaMKII phosphorylation2018

    • Author(s)
      Kimura Yuki、Asa Minori、Urano Yasuomi、Saito Yoshiro、Nishikawa Kiyotaka、Noguchi Noriko
    • Journal Title

      Biochimie

      Volume: 153 Pages: 203-209

    • DOI

      10.1016/j.biochi.2018.07.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selenoprotein P promotes the development of pulmonary arterial hypertension: class FormattedString { value: Possible novel therapeutic target }2018

    • Author(s)
      Kikuchi N, Satoh K, Kurosawa R, Yaoita N, Elias-Al-Mamun M, Siddique MAH, Omura J, Satoh T, Nogi M, Sunamura S, Miyata S, Saito Y, Hoshikawa Y, Okada Y, Shimokawa H.
    • Journal Title

      Circulation

      Volume: 138 Issue: 6 Pages: 600

    • DOI

      10.1161/circulationaha.117.033113

    • URL

      https://localhost/en/publications/c18e6fa7-5ccf-4524-af67-79401c701d14

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PARK7 modulates autophagic proteolysis through binding to the N-terminally arginylated form of the molecular chaperone HSPA52018

    • Author(s)
      Lee Dae-Hee、Kim Daeho、Kim Sung Tae、Jeong Soyeon、Kim Jung Lim、Shim Sang Mi、Heo Ah Jung、Song Xinxin、Guo Zong Sheng、Bartlett David L.、Oh Sang Cheul、Lee Junho、Saito Yoshiro、Kim Bo Yeon、Kwon Yong Tae、Lee Yong J.
    • Journal Title

      Autophagy

      Volume: 14 Issue: 11 Pages: 1870-1885

    • DOI

      10.1080/15548627.2018.1491212

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 6-Hydroxydopamine induces secretion of PARK7/DJ-1 via autophagy-based unconventional secretory pathway2018

    • Author(s)
      Urano Yasuomi、Mori Chinatsu、Fuji Ayano、Konno Keito、Yamamoto Takayuki、Yashirogi Shohei、Ando Mayu、Saito Yoshiro、Noguchi Noriko
    • Journal Title

      Autophagy

      Volume: 14 Issue: 11 Pages: 1943-1958

    • DOI

      10.1080/15548627.2018.1493043

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate its mitochondrial translocation and subsequent mitophagy2018

    • Author(s)
      Shimasaki K, Watanabe-Takahashi M, Umeda M, Funamoto S, Saito Y, Noguchi N, Kumagai K, Hanada K, Tsukahara F, Maru Y, Shibata N, Naito M, Nishikawa K.
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 1 Pages: 22-34

    • DOI

      10.1111/gtc.12544

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnosis of Parkinson's disease and the level of oxidized DJ-1 protein.2018

    • Author(s)
      Yamagishi Y, Saigoh K, Saito Y, Ogawa I, Mitsui Y, Hamada Y, Samukawa M, Suzuki H, Kuwahara M, Hirano M, Noguchi N, Kusunoki S.
    • Journal Title

      Neurosci Res.

      Volume: なし Pages: 58-62

    • DOI

      10.1016/j.neures.2017.06.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models2017

    • Author(s)
      Mita Yuichiro、Nakayama Kaho、Inari Shogo、Nishito Yukina、Yoshioka Yuya、Sakai Naoko、Sotani Kanade、Nagamura Takahiro、Kuzuhara Yuki、Inagaki Kumi、Iwasaki Miki、Misu Hirofumi、Ikegawa Masaya、Takamura Toshinari、Noguchi Noriko、Saito Yoshiro
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1658-1658

    • DOI

      10.1038/s41467-017-01863-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eicosapentaenoic acid down-regulates expression of the selenoprotein P gene by inhibiting SREBP-1c protein independently of the AMP-activated protein kinase pathway in H4IIEC3 hepatocytes.2017

    • Author(s)
      Tajima-Shirasaki N, Ishii KA, Takayama H, Shirasaki T, Iwama H, Chikamoto K, Saito Y, Iwasaki Y, Teraguchi A, Lan F, Kikuchi A, Takeshita Y, Murao K, Matsugo S, Kaneko S, Misu H, Takamura T.
    • Journal Title

      J Biol Chem.

      Volume: 292 Issue: 26 Pages: 10791-10800

    • DOI

      10.1074/jbc.m116.747006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 必須微量元素セレンの代謝と疾患ー高血糖予測マーカーとしての可能性2019

    • Author(s)
      斎藤芳郎
    • Organizer
      第41回 東北薬学セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] “Biology and Pharmaceutical Sciences of Essential Trace Element “Selenium” Development of Novel Prophylaxis for Type 2 Diabetes”2019

    • Author(s)
      Yoshiro Saito
    • Organizer
      International Symposium on Pharmaceutical Sciences in Sendai 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] “Selenoprotein P as a regulator of pancreatic beta cell function-Association between the pancreas and liver”2019

    • Author(s)
      Yoshiro Saito
    • Organizer
      8th International Selenium Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 必須微量元素セレンの代謝と疾患-レドックス制御の破綻と酸化/還元ストレス2019

    • Author(s)
      斎藤芳郎
    • Organizer
      第20回 脳研×高度先進×COI合同セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 過剰セレノプロテインPを標的としたテーラーメイド2型糖尿病治療の開発-インスリン抵抗性およびインスリン分泌の改善2019

    • Author(s)
      斎藤芳郎
    • Organizer
      Scientific Exchange Meeting in 金沢
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] "Selenoprotein P and diabetes: Its excess and pancreatic toxicity”2019

    • Author(s)
      Yoshiro Saito
    • Organizer
      13th International Society for Trace Element Research in Humans (ISTERH2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生体内におけるセレン代謝とエネルギー産生2019

    • Author(s)
      斎藤芳郎
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] “Selenoprotein P as a significant redox regulator in vivo: Relevance to pancreatic beta cell function”2019

    • Author(s)
      Yoshiro Saito
    • Organizer
      1st STINT-JSPS Joint Symposium, Session “Redox Biology for Human Health”
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] “Selenoprotein and lipid oxidation- Disorders related to its deficiency and excess”2019

    • Author(s)
      Yoshiro Saito
    • Organizer
      Japan-Aston symposium on lipid oxidation in inflammation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 「血漿セレン含有タンパク質セレノプロテインPによるレドックス制御と膵β細胞の機能」2019

    • Author(s)
      斎藤芳郎
    • Organizer
      第72回 日本酸化ストレス学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 「血漿セレン含有タンパク質セレノプロテインPのセレン運搬メカニズムと疾患」2019

    • Author(s)
      斎藤芳郎
    • Organizer
      第36回 日本微量栄養素学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 「ビタミンE類の多様な抗酸化作用ー必須微量元素セレンとの関わり」2019

    • Author(s)
      斎藤芳郎
    • Organizer
      第362回 脂溶性ビタミン総合研究委員会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 生体内レドックス制御因子セレノプロテインPの機能と疾患2019

    • Author(s)
      斎藤芳郎
    • Organizer
      平成30年度文部科学省私立大学研究ブランディング事業・研究成果報告会・シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 血漿セレン含有タンパク質セレノプロテインPによる膵β細胞障害および中和抗体による抑制:糖尿病モデル動物への効果2018

    • Author(s)
      斎藤芳郎、三田雄一郎、稲荷尚吾、長村 尭浩、北原那美、御簾博文、篁俊成、野口範子
    • Organizer
      第71回日本酸化ストレス学会・第18回日本NO学会合同学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Selenoprotein P as a regulator of pancreatic beta cell function: Improving effects of neutralizing antibody.2018

    • Author(s)
      Yoshiro Saito, Yuichiro Mita, Shogo Inari, Takahiro Nagamura, Hirofumi Misu, Toshinari Takamura, and Noriko Noguchi
    • Organizer
      19th SFRRI Biennial Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生活習慣病と抗酸化タンパク質セレノプロテインP:ホメオスタシスにおける活性酸素の功罪2018

    • Author(s)
      斎藤芳郎
    • Organizer
      第26回日本運動生理学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Selenoprotein P as a significant redox regulator in vivo: implication of its excess and diabetes2018

    • Author(s)
      Yoshiro Saito
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Selenoprotein P as a significant regulator of Pancreatic beta cell function2018

    • Author(s)
      Yoshiro Saito
    • Organizer
      2018 Fall International Convention of The Pharmaceutical Society of Korea
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 血漿セレン含有タンパク質セレノプロテインP研究の新展開ーセレン代謝と疾患2018

    • Author(s)
      斎藤芳郎
    • Organizer
      メタルバイオサイエンス研究会2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 2型糖尿病の治療に新たな知見ー世界初 インスリン産生とインスリン抵抗性の両方を改善する物質を発見2018

    • Author(s)
      斎藤芳郎
    • Organizer
      第2回 同志社メディアセミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] セレノプロテインPのレドックス制御機能と疾患―膵β細胞における二面性2018

    • Author(s)
      斎藤芳郎
    • Organizer
      第15回 レドックス・ライフイノベーション シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] セレノプロテインPのセレン運搬作用と膵β細胞のレドックス制御2018

    • Author(s)
      斎藤芳郎
    • Organizer
      日本薬学会 第128年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血漿セレン含有タンパク質セレノプロテインPの膵β細胞における二面性2017

    • Author(s)
      斎藤芳郎
    • Organizer
      第28回 日本微量元素学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血漿セレン含有タンパク質セレノプロテインPの機能と疾患ーレドックスバランスと膵β細胞の機能2017

    • Author(s)
      斎藤芳郎
    • Organizer
      第90回 日本生化学会・第40回 日本分子生物学会年会(ConBio2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] Vitamin E: Chemistry and Nutritional Benefits.2018

    • Author(s)
      Yoshiro Saito and Yasukazu Yoshida
    • Total Pages
      12
    • Publisher
      Royal Society of Chemistry
    • ISBN
      9781788016216
    • Related Report
      2018 Annual Research Report
  • [Book] レドックス疾患学 セレノプロテインPによるレドックス制御と2型糖尿病2018

    • Author(s)
      斎藤芳郎、野口範子、御簾博文、篁俊成
    • Total Pages
      6
    • Publisher
      羊土社
    • ISBN
      9784758103695
    • Related Report
      2017 Annual Research Report
  • [Remarks] 研究内容

    • URL

      http://www.pharm.tohoku.ac.jp/~taisya/outline/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究成果

    • URL

      http://www.pharm.tohoku.ac.jp/~taisya/research/index.html

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2022-12-28  

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