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Cross talk of insulin resistance and vitamin A metabolism

Research Project

Project/Area Number 23617038
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrated Nutrition Science
Research InstitutionNational Institute of Health and Nutrition

Principal Investigator

YAMAUCHI Jun  独立行政法人国立健康・栄養研究所, 食品栄養・表示研究室, 室長 (80312297)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsビタミンA / インスリン抵抗性 / RBP4 / 脂肪細胞 / 糖尿病 / 代謝
Research Abstract

Retinol binding protein 4 (RBP4) is the transport protein that carries retinol in blood. Mice lacking glucose transporter 4 (GLUT4) in adipocytes have enhanced Rbp4 gene expression; however, the molecular mechanism is unknown. We found a G4KA (GLUT4 knockdown-dependent transcriptional activation) element located 1.3 kb upstream of the Rbp4 promoter. In a yeast one-hybrid screen of a G4KD-L1 (GLUT4 knockdown 3T3-L1) adipocyte cell cDNA library, using the G4KA element as bait, we identified subunit of the 20 S proteasome, PSMB1. PSMB1 was tightly bound to G4KA. PSMB1 RNA interference inhibited Rbp4 transcription. Nuclear transportation of PSMB1 was increased in G4KD-L1 cells. The putative tyrosine phosphorylation site in PSMB1 was mutated to phenylalanine (Y149F). Y149F PSMB1 displayed increased nuclear translocation, resulting in activation of transcription in adipocytes. We propose that modulation of PSMB1 nuclear localization can be influenced by the phosphorylation status of PSMB1.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (38 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (21 results) (of which Invited: 2 results) Book (4 results) Remarks (3 results)

  • [Journal Article] Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women2014

    • Author(s)
      Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y
    • Journal Title

      J Bone Miner Metab

      Volume: 32(2) Pages: 142-50

    • Related Report
      2013 Final Research Report
  • [Journal Article] Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women.2014

    • Author(s)
      Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y.
    • Journal Title

      J Bone Miner Metab.

      Volume: 32 Issue: 2 Pages: 142-150

    • DOI

      10.1007/s00774-013-0472-7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of nuclear localization of PSMB1 in transcriptional activation2013

    • Author(s)
      Yamauchi J, Sekiguchi M, Shirai T, Yamada M, Ishimi Y
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 77(8) Pages: 1785-7

    • NAID

      10031195836

    • Related Report
      2013 Final Research Report
  • [Journal Article] Dietary Reference Intakes for Japanese 20102013

    • Author(s)
      Yoshida M、Kikunaga S、Yamauchi J、T.Utsugi M、Kodama H、Morita A、Esashi T
    • Journal Title

      Microminerals J Nutr Sci Vitaminol

      Volume: 59

    • Related Report
      2013 Final Research Report
  • [Journal Article] Role of nuclear localization of PSMB1 in transcriptional activation.2013

    • Author(s)
      Yamauchi J, Sekiguchi M, Shirai T, Yamada M, Ishimi Y.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 77 Pages: 1785-1787

    • NAID

      10031195836

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dietary Reference Intakes for Japanese 2010:Microminerals2013

    • Author(s)
      Yoshida M、Kikunaga S、Yamauchi J、T.Utsugi M、Kodama H、Morita A、Esashi T
    • Journal Title

      J Nutr Sci Vitaminol

      Volume: 59

    • NAID

      130003368191

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vitamin D receptor is not essential for extracellular signal-related kinase phosphorylation by vitamin D(3) in human Caco-2/TC7 cells2012

    • Author(s)
      Yamauchi J, Sekiguchi M, Shirai T, Ishimi Y
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 76(8) Pages: 1588-90

    • NAID

      130004137939

    • Related Report
      2013 Final Research Report
  • [Journal Article] Vitamin D receptor is not essential for extracellular signal-related kinase phosphorylation by vitamin D(3) in human Caco-2/TC7 cells.2012

    • Author(s)
      Yamauchi J, Sekiguchi M, Shirai T, Ishimi Y.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 76 Pages: 1588-1590

    • NAID

      130004137939

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] AICAR response element binding protein (AREBP), a key modulator of hepatic glucose production regulated by AMPK in vivo2011

    • Author(s)
      Shirai T, Inoue E, Ishimi Y, Yamauchi J
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 414(2) Pages: 287-91

    • Related Report
      2013 Final Research Report
  • [Journal Article] AICAR response element binding protein (AREBP), a key modulator of hepatic glucose production regulated by AMPK in vivo.2011

    • Author(s)
      Shirai T, Inoue E, Ishimi Y, Yamauchi J.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 414 Issue: 2 Pages: 287-291

    • DOI

      10.1016/j.bbrc.2011.08.120

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 食品表示について2014

    • Author(s)
      山内淳
    • Organizer
      第17回日本病態栄養学会年次学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2014-01-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women2013

    • Author(s)
      Koitaya N、Sekiguchi、Tousen Y、Nishide N、Morita A、Yamauchi J、Gando Y、Miyachi M、Aoki M、Komatsu M、Watanabe F、Morishita K、Ishimi Y
    • Organizer
      The 2nd Joint Meeting of International Bone Mineral Society and Japanese Society for Bone and Mineral Research
    • Place of Presentation
      Kobe
    • Year and Date
      2013-06-01
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] ビタミンDによるMAPキナーゼ活性化のメカニズム2013

    • Author(s)
      関口真理子、白井智美、石見佳子、山内淳
    • Organizer
      第67回日本栄養・食糧学会大会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] BCMO1遺伝子のレチノイン酸による発現制御機構の解析2013

    • Author(s)
      白井智美、白鳥明日香、石見佳子、山内淳
    • Organizer
      第67回日本栄養・食糧学会大会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 1年間のビタミンK2(MK-4)補給摂取が閉経後女性の骨代謝に及ぼす影響2012

    • Author(s)
      小板谷典子、東泉裕子、西出依子、森田明美、山内淳、青木麻実、石見佳子
    • Organizer
      第59回日本栄養改善学会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖新生系酵素遺伝子発現を制御する新規転写因子AREBPの生体機能2012

    • Author(s)
      白井智美、石見佳子、山内淳
    • Organizer
      第66回日本栄養・食糧学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2012-05-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 1年間のビタミンK2(メナキノン-4)補給摂取が閉経後女性の骨代謝に及ぼす影響2011

    • Author(s)
      石見佳子、小板谷典子、東泉裕子、西出依子、森田明美、山内淳、青木麻実
    • Organizer
      第59回日本栄養改善学会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] β-カロテン開裂酵素BCMO1のレチノイン酸による遺伝子発現制御機構の解析2011

    • Author(s)
      山内淳、白鳥明日香、石見佳子
    • Organizer
      日本ビタミン学会第63回大会
    • Place of Presentation
      広島
    • Year and Date
      2011-06-04
    • Related Report
      2013 Final Research Report
  • [Presentation] βカロテンからレチナールへの変換に関わる酵素BCMO1のレチノイン酸による遺伝子発現制御機構の解析2011

    • Author(s)
      白鳥明日香、小林謙一、山本祐司、田所忠弘、山内淳
    • Organizer
      第65回日本栄養・食糧学会大会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-15
    • Related Report
      2013 Final Research Report
  • [Presentation] ビタミンDのMAPキナーゼを介した作用発現メカニズムの解析2011

    • Author(s)
      関口真理子、山内淳
    • Organizer
      第65回日本栄養・食糧学会大会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-15
    • Related Report
      2013 Final Research Report
  • [Presentation] βカロテンからレチナールへの変換に関わる酵素BCMO1のレチノイン酸による遺伝子発現制御機構の解析2011

    • Author(s)
      白鳥明日香、小林謙一、山本祐司、田所忠弘、山内淳
    • Organizer
      第65回日本栄養・食糧学会大会
    • Place of Presentation
      お茶の水女子大学(東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] ビタミンDのMAPキナーゼを介した作用発現メカニズムの解析2011

    • Author(s)
      関口真理子、山内淳
    • Organizer
      第65回日本栄養・食糧学会大会
    • Place of Presentation
      お茶の水女子大学(東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] β-カロテン開裂酵素BCMO1のレチノイン酸による遺伝子発現制御機構の解析2011

    • Author(s)
      山内淳、白鳥明日香、石見佳子
    • Organizer
      日本ビタミン学会第63回大会
    • Place of Presentation
      安田女子大学(広島)
    • Related Report
      2011 Research-status Report
  • [Presentation] 転写因子PSMB1の核内移行によるRBP4遺伝子発現調節機構

    • Author(s)
      関口真理子、白井智美、山田麻未、石見佳子、山内淳
    • Organizer
      第68回日本栄養・食糧学会
    • Place of Presentation
      北海道(酪農学園大学)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 食品表示について

    • Author(s)
      山内淳
    • Organizer
      第17回日本病態栄養学会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ビタミンDによるMAPキナーゼ活性化のメカニズム

    • Author(s)
      関口真理子、白井智美、石見佳子、山内淳
    • Organizer
      第67回日本栄養・食糧学会大会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] BCMO1遺伝子のレチノイン酸による発現制御機構の解析

    • Author(s)
      白井智美、白鳥明日香、石見佳子、山内淳
    • Organizer
      第67回日本栄養・食糧学会大会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 糖新生系酵素遺伝子発現を制御する新規転写因子AREBPの生体機能

    • Author(s)
      白井智美、石見佳子、山内淳
    • Organizer
      日本栄養・食糧学会大会
    • Place of Presentation
      仙台 東北大学
    • Related Report
      2012 Research-status Report
  • [Presentation] 1年間のビタミンK2(MK-4)補給摂取が閉経後女性の骨代謝に及ぼす影響

    • Author(s)
      小板谷典子、東泉裕子、西出依子、森田明美、山内淳、青木麻実、石見佳子
    • Organizer
      日本栄養改善学会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] 食品保健制度の現状と課題 -特に食品表示について-

    • Author(s)
      山内淳
    • Organizer
      日本食生活学会
    • Place of Presentation
      東京 跡見学園女子大学
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 脂溶性ビタミンと食品表示制度

    • Author(s)
      山内淳
    • Organizer
      脂溶性ビタミン総合研究委員会
    • Place of Presentation
      東京 帝京大学
    • Related Report
      2012 Research-status Report
  • [Book] トコトリエノール研究:過去から現在へ栄養学レビュー(翻訳); 21(3)2013

    • Author(s)
      山内淳
    • Related Report
      2013 Final Research Report
  • [Book] 食品保健制度の現状と課題‐特に食品表示について‐日本食生活学会誌; 24(1)2013

    • Author(s)
      山内淳
    • Related Report
      2013 Final Research Report
  • [Book] 特別企画基礎から制度改革まで「食品表示」をおさえる月刊糖尿病ライフさかえ, 53(8)2013

    • Author(s)
      山内淳
    • Publisher
      (公社)日本糖尿病協会
    • Related Report
      2013 Final Research Report
  • [Book] 機能性食品の作用と安全性百科;骨系に作用する成分、生殖系に作用する成分2012

    • Author(s)
      石見佳子、山内淳、竹林純
    • Total Pages
      384
    • Publisher
      丸善出版
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www0.nih.go.jp/eiken/

    • Related Report
      2013 Final Research Report
  • [Remarks] 独立行政法人 国立健康・栄養研究所

    • URL

      http://www0.nih.go.jp/eiken/

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www0.nih.go.jp/eiken/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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