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TNFa変換酵素を介したインスリン抵抗性発現機序の解析

Research Project

Project/Area Number 22590987
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKumamoto University

Principal Investigator

MOTOSHIMA Hiroyuki  熊本大学, 医学部附属病院, 助教 (40398201)

Co-Investigator(Kenkyū-buntansha) MATSUMURA Takeshi  熊本大学, 医学部附属病院, 講師 (20398192)
NISHIKAWA Takeshi  熊本大学, 生命科学研究部, 准教授 (70336212)
KONDO Tatsuya  熊本大学, 生命科学研究部, 助教 (70398204)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肥満 / 糖尿病 / インスリン抵抗性 / TNFa 変換酵素(TACE) / ストレスキナーゼ / インスリンシグナル伝達 / TNFa産生 / 発現制御 / 細胞・組織 / シグナル伝達 / 蛋白質
Research Abstract

T umor necrosis factor (TNF) converting enzyme (TACE)cleaves the transmembrane precursor of TNF and produces mature TNF , which is aproinflammatory cytokine and one of the major mediators of obesity- and diabetes-inducedinsulin resistance. However , the regulation of TACE activity and expression ininsulin-sensitive tissues in obesity has not been fully determined. In the presentinvestigation, we found the adipose tissue-specific upregulation of TACE activity andexpression induced by obesity and the downregulation by caloric restriction in KKAy mice.In addition, we found that the activation of several stress-kinases may involve in theupreglation of TACE function in adipose tissue of obese mice.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (27 results)

All 2013 2012 2011 2010

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (11 results)

  • [Journal Article] Apocynin suppresses theprogression of atherosclerosis inapoE-deficient mice by inactivationof macrophages2013

    • Author(s)
      Kinoshita H, Matsumura T, Ishii N,Fukuda K, Senokuchi T, Motoshima H,Kondo T, Taketa K, Kawasaki S,Hanatani S, Takeya M, Nishikawa T,Araki E
    • Journal Title

      Biochem Biophys ResCommun

      Volume: 431 Pages: 124-30

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of TNFαconverting enzyme activity invisceral adipose tissue of obese mice2013

    • Author(s)
      Kawasaki S, Motoshima H, Hanatani S,Takaki Y, Igata M, Tsutsumi A,Matsumura T, Kondo T, Senokuchi T,Ishii N, Kinoshita H, Fukuda K,Kawashima J, Shimoda S, NishikawaT, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 430 Pages: 1189-94

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of TNFα converting enzyme activity in visceral adipose tissue of obese mice2013

    • Author(s)
      川崎修二
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 430 Issue: 4 Pages: 1189-1194

    • DOI

      10.1016/j.bbrc.2012.12.086

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages2013

    • Author(s)
      木下博之
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 431 Issue: 2 Pages: 124-130

    • DOI

      10.1016/j.bbrc.2013.01.014

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thiazolidinedione-independent activation of peroxisome proliferator activated receptor is a potential target for diabetic macrovascularcomplications2012

    • Author(s)
      Matsumura T, Taketa K, Shimoda S, ArakiE
    • Journal Title

      J Diabetes Invest

      Volume: 3 Pages: 11-23

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hyperthermia With MildElectrical Stimulation ProtectsPancreatic ss-Cells From Cell Stressesand Apoptosis2012

    • Author(s)
      Kondo T, Sasaki K, Matsuyama R,Morino-Koga S, Adachi H, Suico MA,Kawashima J, Motoshima H, Furukawa N,Kai H, Araki E
    • Journal Title

      Diabetes

      Volume: 61 Pages: 837-847

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacotherapeutic Options for thePrevention of Cardiovascular Disease inPatients with Type 2 Diabetes2012

    • Author(s)
      Taketa K, Matsumura T, Furukawa N ArakiE
    • Journal Title

      ClinicalMedicine Reviews in Vascular Health

      Volume: 4 Pages: 43-53

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-atherosclerotic Potential ofDihydropyridine Calcium ChannelBlockers2012

    • Author(s)
      Ishii N, Matsumura T, Shimoda S, ArakiE
    • Journal Title

      J Atheroscler Thromb

      Volume: 19 Pages: 693-704

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caloricrestriction decreases ER stress inliver and adipose tissue in ob/ob mice2011

    • Author(s)
      Tsutsumi A, Motoshima H, Kondo T,Kawasaki S, Matsumura T, Hanatani S,Igata M, Ishii N, Kinoshita H, KawashimaJ, Taketa K, Furukawa N, Tsuruzoe K,Nishikawa T, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 404 Pages: 339-344

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glucose uptakein rat skeletal muscle L6 cells isincreased by low-intensity electricalcurrent through the activation of thephosphatidylinositol-3-OH kinase(PI-3K)/Akt pathway2011

    • Author(s)
      Yano S, Morino-Koga S, Kondo T, Suico MA,Koga T, Shimauchi Y, Matsuyama S, ShutoT, Sato T, Araki E, Kai H
    • Journal Title

      J Pharmacol Sci

      Volume: 115 Pages: 94-98

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Telmisartan exerts antiatheroscleroticeffects by activating peroxisomeproliferator-activated receptor-r inmacrophages2011

    • Author(s)
      Matsumura T, Kinoshita H, Ishii N,Fukuda K, Motoshima H, Senokuchi T,Take ta K, Ka was aki S, N ish im aki- Mog ami T,Kawada T, Nishikawa T, Araki E
    • Journal Title

      Arterioscler Thromb VascBiol

      Volume: 31 Pages: 1268-1275

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Angptl4 deficiencydecreases serum triglyceride levels in low-density lipoprotein receptorknockout mice and streptozotocin-induceddiabetic mice2011

    • Author(s)
      Adachi H, Kondo T, Koh GY, Nagy A, OikeY, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 409 Pages: 177-180

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heat shockresponse regulates insulin sensitivityand glucose homeostasis:pathophysiological impact andtherapeutic potential2011

    • Author(s)
      Kondo T, Koga S, Matsuyama R, MiyagawaK, Goto R, Kai H, Araki E
    • Journal Title

      Curr DiabetesRev

      Volume: 7 Pages: 264-269

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caloric restriction decreases ER stress in liver and adipose tissue in ob/ob mice.2011

    • Author(s)
      Tsutsumi A
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 404 Pages: 339-344

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nifedipine induces peroxisome proliferator-activated receptor-gamma activation in macrophages and suppresses the progression of athero-sclerosis in apolipoprotein E-deficient mice.2010

    • Author(s)
      Ishii N
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 30 Pages: 1598-1605

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice.2010

    • Author(s)
      Adachi H
    • Journal Title

      Am J Physiol Endocrinol Metab.

      Volume: 299

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 肥満・糖尿病モデルにおけるTNF-α converting enzyme活性制御‐カロリー制限とJNK抑制の効果2012

    • Author(s)
      川崎修二
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜市パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] 脂肪組織におけるTNF-α converting enzyme (TACE) の発現制御‐JNKおよびPKCの関与2012

    • Author(s)
      川崎修二
    • Organizer
      第62回日本体質医学会総会
    • Place of Presentation
      大阪市大阪国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] DPP-4阻害薬シタグリプチンの血糖コントロールおよび血圧への影響の解析-1年間投与症例における後ろ向き調査-2012

    • Author(s)
      本島寛之
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜市パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] 悪性腫瘍合併糖尿病患者における血糖コントロール指標としての血中可溶性インスリン受容体の意義2012

    • Author(s)
      井形元維
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] TNF-α Up-regulates TNF-α Converting Enzyme (TACE) in Visceral Adipose Tissues via JNK and PKC Activation2012

    • Author(s)
      本島寛之
    • Organizer
      The 48th Annual Meeting of the Europian Association for the Study of Diatebes
    • Place of Presentation
      ドイツ・ベルリン ベルリンコンベンションセンター
    • Related Report
      2012 Annual Research Report
  • [Presentation] Obesity Up-regulates TNF-α Converting Enzyme (TACE) in Visceral Adipose Tissues via JNK and PKC Activation2012

    • Author(s)
      川崎修二
    • Organizer
      The 72th Annual Meeting of American Diabetes Association
    • Place of Presentation
      アメリカ合衆国・フィラデルフィア フィラデルフィアコンベンションセンター
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肥満・糖尿病モデルにおけるTNF-α converting enzymeの制御機構と食餌制限の効果2011

    • Author(s)
      川崎修二
    • Organizer
      第23回分子糖尿病学シンポジウム
    • Place of Presentation
      くまもと県民交流館パレア(熊本県)
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖尿病におけるTNF-α converting enzyme発現調節2011

    • Author(s)
      川崎修二
    • Organizer
      第49回日本糖尿病学会九州地方会
    • Place of Presentation
      アクロス福岡(福岡県)
    • Year and Date
      2011-10-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 食餌制限は肥満・糖尿病モデル動物においてTNF-α converting enzymeの発現を軽減させる2011

    • Author(s)
      川崎修二
    • Organizer
      第61回日本体質医学会総会
    • Place of Presentation
      TKP東京駅日本橋ビジネスセンター(東京都)
    • Year and Date
      2011-10-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] 血糖指標としての血中可溶性インスリン受容体-ステロイドによる糖代謝悪化を検出できるのか?-2011

    • Author(s)
      本島寛之
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌プリンスホテル国際館パミール(北海道)
    • Year and Date
      2011-05-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] 短期血糖コントロール指標としての血中可溶性インスリン受容体αサブユニットの有用性2010

    • Author(s)
      本島寛之
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2010-05-28
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2021-04-07  

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