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Proteomic Analysis of Serum Biomarkers for Pre-diabetes

Research Project

Project/Area Number 25461370
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Unoki-Kubota Hiroyuki  国立研究開発法人国立国際医療研究センター, その他部局等, 室長 (40323290)

Co-Investigator(Kenkyū-buntansha) KABURAGI Yasushi  国立国際医療研究センター, 研究所, 部長 (40342927)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords2型糖尿病 / プロテオーム / SERPINA3
Outline of Final Research Achievements

To identify early diagnostic markers for type 2 diabetes mellitus (T2DM) that are maintained throughout a diabetic phenotype, we performed serum proteomic analysis, and identified serine (or cysteine) peptidase inhibitor, clade A, member 3 (SERPINA3) as one of the candidate biomarkers for T2DM. We further validated the differential expression of SERPINA3 both in LEA rat, a spontaneous animal model of T2DM without obesity, and in human T2DM patients. SERPINA3 were increased significantly in the sera of LEA rats compared with age-matched BN rats at all three time points (8-24 week-old). Serum levels of SERPINA3 were significantly higher also in T2DM patients than in healthy control subjects. In multiple linear regression analysis, HbA1c, estimated glomerular filtration rate, and the homeostasis model assessment index of insulin resistance were independently associated with SERPINA3 levels. These findings suggest a possible role for SERPINA3 in the development of the early stages of T2DM.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (27 results)

All 2015 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (19 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Increased serum leukocyte cell-derived chemotaxin 2 (LECT2) levels in obesity and fatty liver2013

    • Author(s)
      Okumura A, Unoki-Kubota H, Matsushita Y, Shiga T, Moriyoshi Y, Yamagoe S, Kaburagi Y
    • Journal Title

      BioScience Trends.

      Volume: 7(6) Pages: 276-283

    • NAID

      130003397274

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential proteome analysis of serum proteins associated with the development of type 2 diabetes mellitus in the KK-Ay mouse model using the iTRAQ technique.2013

    • Author(s)
      Takahashi E, Okumura A, Unoki-Kubota H, Hirano H, Kasuga M, Kaburagi Y.
    • Journal Title

      J Proteomics.

      Volume: 84C Pages: 40-51

    • DOI

      10.1016/j.jprot.2013.03.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Leukocyte cell-derived chemotaxin 2 is a zinc-binding protein2013

    • Author(s)
      Okumura A, Suzuki T, Miyatake H, Okabe T, Hashimoto Y, Miyakawa T, Zheng H, Unoki-Kubota H, Ohno H, Dohmae N, Kaburagi Y, Miyazaki Y, Tanokura M, Yamagoe S
    • Journal Title

      FEBS Lett

      Volume: 587 Issue: 5 Pages: 404-409

    • DOI

      10.1016/j.febslet.2013.01.025

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 非標識定量プロテオミクス法による糖尿病腎症関連尿マーカーの探索2015

    • Author(s)
      久保田浩之、高橋枝里、本田律子、志賀智子、奥村彰規、梶尾裕、野田光彦、鏑木康志
    • Organizer
      第30回日本糖尿病合併症学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 網膜周皮細胞の分泌ペプチドーム解析で得られた新規鎖長ペプチドΔADTの機能解析2015

    • Author(s)
      奥村彰規、高橋枝里、久保田浩之、鏑木康志
    • Organizer
      第30回日本糖尿病合併症学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Label-free quantitative urinary proteomic analysis for discovering biomarkers of diabetic nephropathy2015

    • Author(s)
      Unoki-Kubota H, Takahashi E, Yamamoto-Honda R, Shiga T, Okumura A, Kajio H, Noda M, Kaburagi Y
    • Organizer
      Keystone symposia Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
    • Place of Presentation
      京都
    • Year and Date
      2015-10-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非肥満性2型糖尿病モデルラットLEAラットの血清プロテオーム解析による2型糖尿病関連因子の探索2015

    • Author(s)
      高橋枝里、久保田浩之、清水有紀子、奥村彰規、岡村匡史、本田律子、梶尾裕、野田光彦、鏑木康志
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 尿中serine protease inhibitor A3と糖尿病腎症との関連の検討2015

    • Author(s)
      久保田浩之、高倉美智子、奥村彰規、高橋枝里、岩田和希子、本田律子、梶尾裕、野田光彦、鏑木康志
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 網膜周皮細胞の分泌ペプチドーム解析と網膜毛細血管内皮細胞への役割解析2015

    • Author(s)
      奥村彰規、高橋枝里、久保田浩之、鏑木康志
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非肥満性2型糖尿病モデルラットLEAラット血清を用いた2型糖尿病関連蛋白質の探索2015

    • Author(s)
      高橋枝里、久保田浩之、清水有紀子、奥村彰規、岡村匡史、本田律子、梶尾裕、野田光彦、鏑木康志
    • Organizer
      第52回日本臨床分子医学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Serum leukocyte cell-derived chemotaxin 2 levels are decreased in patients with diabetic retinopathy2014

    • Author(s)
      Okumura A, Unoki-Kubota H, Matsushita Y, Shiga T, Yamamoto-Honda R, Kajio H, Noda M, Kaburagi Y
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Proteomic Analysis of Serum Proteins in LEA Rat, a New Rat Model of Nonobese Type 2 Diabetes Mellitus2014

    • Author(s)
      Takahashi E, Unoki-Kubota H, Shimizu Y, Okumura A, Okamura T, Noda M, Kaburagi Y
    • Organizer
      American Diabetes Association 74th Scientific Sessions
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-06-13 – 2014-06-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 糖尿病腎症患者における血清可溶性LDL receptor relative with eleven binding repeats濃度の検討2014

    • Author(s)
      久保田 浩之、岩田 和希子、奥村 彰規、姜 美子、梶尾 裕、野田 光彦、鏑木 康志
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 血中タンパク質LECT2の糖尿病網膜症患者における血中濃度と網膜毛細血管内皮細胞への影響2014

    • Author(s)
      奥村 彰規、久保田 浩之、松下 由実、本田 律子、梶尾 裕、野田 光彦、鏑木 康志
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 非標識定量プロテオミクス法を用いた糖尿病腎症早期診断マーカーの探索2014

    • Author(s)
      高倉 美智子、久保田 浩之、本田 律子、梶尾 裕、野田 光彦、鏑木 康志
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Leukocyte cell-derived chemotaxin 2 is a zinc-binding protein: the monomeric forms are stabilized by the zinc ion2013

    • Author(s)
      Okumura A, Suzuki T, Miyatake H, Miyakawa T, Zheng H, Unoki-Kubota H, Dohmae N, Kaburagi Y, Tanokura M, Yamagoe S
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] 血中LECT2濃度は肥満と脂肪肝の予測因子となりうるか2013

    • Author(s)
      奥村 彰規、久保田 浩之、松下 由実、志賀 智子、森吉 百合子、鏑木 康志
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 定量的プロテオミクスを用いた2型糖尿病関連因子の探索2013

    • Author(s)
      久保田 浩之、高橋 枝里、奥村 彰規、平野 久、鏑木 康志
    • Organizer
      第28回日本糖尿病合併症学会
    • Place of Presentation
      旭川
    • Related Report
      2013 Research-status Report
  • [Presentation] Electrostatic Repulsion-Hydrophilic Interaction Chromatography for Profiling of Human Urine Shotgun Proteome2013

    • Author(s)
      Takakura M, Unoki-Kubota H, Kaburagi Y
    • Organizer
      HUPO 12th Annual World Congress
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] iTRAQ-Based Quantitation and Validation by Multiple Reaction Monitoring to Identify Diabetes-Related Biomarkers in Sera from KK-Ay Diabetes Mice2013

    • Author(s)
      Takahashi E, Unoki-Kubota H, Okumura A, Hirano H, Kaburagi Y
    • Organizer
      HUPO 12th Annual World Congress
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Leukocyte cell-derived chemotaxin 2は新規の肥満関連因子である2013

    • Author(s)
      奥村 彰規、久保田 浩之、松下 由実、志賀 智子、森吉 百合子、鏑木 康志
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 蛍光ディファレンシャル二次元電気泳動による糖尿病腎症患者のプロテオーム解析2013

    • Author(s)
      鏑木 康志、山下 亮、本間 綾香、梶尾 裕、野田 光彦、久保田 浩之
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Book] AGEsと老化-糖化制御からみたウェルエイジング-2013

    • Author(s)
      久保田 浩之、山岸 昌一
    • Total Pages
      278
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Research-status Report
  • [Remarks] 国立研究開発法人国立国際医療研究センター 研究所 糖尿病研究センター 臓器障害研究部

    • URL

      http://www.ncgm-dmcomp.umin.jp

    • Related Report
      2015 Annual Research Report
  • [Remarks] 国立研究開発法人国立国際医療研究センター研究所 糖尿病研究センター臓器障害研究部ホームページ

    • URL

      http://www.ncgm-dmcomp.umin.jp

    • Related Report
      2014 Research-status Report
  • [Remarks] 独立行政法人国立国際医療研究センター 糖尿病研究センター 臓器障害研究部ホームページ

    • URL

      http://www.ncgm-dmcomp.umin.jp

    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 糖尿病腎症の発症または発症リスクの検出方法及びキット2013

    • Inventor(s)
      鏑木 康志、久保田 浩之、高倉 美智子
    • Industrial Property Rights Holder
      鏑木 康志、久保田 浩之、高倉 美智子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-173382
    • Filing Date
      2013-08-23
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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