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2011 Fiscal Year Final Research Report

Regulation of pancreatic beta cell mass via glucokinase-dependent and independent pathways

Research Project

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Project/Area Number 21390282
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionYokohama City University

Principal Investigator

TERAUCHI Yasuo  横浜市立大学, 医学研究科, 教授 (40359609)

Co-Investigator(Kenkyū-buntansha) KIMURA Mari  横浜市立大学, 附属病院, 准教授 (40363840)
AOKI Kazutaka  横浜市立大学, 医学部, 助教
Project Period (FY) 2009 – 2011
Keywordsグルコキナーゼ / インスリン抵抗性 / 膵β細胞 / グルコキナーゼ活性化薬 / IRS-2
Research Abstract

GKA-stimulated IRS2 production affected beta cell proliferation. Oxidative stress diminished the effects of GKA on the changes in expression of genes involved in beta cell function and proliferation. GKA was able to ameliorate ER stress-mediated apoptosis via both IRS-2-dependent pathway and IRS-2-independent regulation of the expressions of genes related to ER stress. Partial pancreatectomy is a good model for the evaluation of adaptive proliferation ofβcells in rodents. We investigated the roles of glucokinase and IRS-2 in these mouse models and noted that neither glucokinase nor IRS-2 was required forβcell proliferation after partial pancreatectomy. Collectively, we investigated the regulation of pancreaticβcell mass via glucokinase-dependent and. independent pathways.

  • Research Products

    (41 results)

All 2012 2011 2010 2009 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (23 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Effects of liraglutide onβcell-specific glucokinase-deficient neonatal mice2012

    • Author(s)
      Shirakawa J, Tanami R, Togashi Y, Tajima K, Orime K, Kubota N, Kadowaki T, Goshima Y, Terauchi T
    • Journal Title

      Endocrinology

    • Peer Reviewed
  • [Journal Article] Plasminogen activator inhibitor-1 is associated with renal dysfunction independent of BMI and serum lipid levels in patients with type 2 diabetes2012

    • Author(s)
      Shirakawa J, Togashi Y, Tajima K, Orime K, Kikuchi K, Miyazaki T, Sato K, Kimura M, Goshima Y, Terauchi Y
    • Journal Title

      Diabetes Res. Clin. Pract

    • Peer Reviewed
  • [Journal Article] Control of beta cell function and proliferation in mice stimulated by small molecule glucokinase activator under various conditions2012

    • Author(s)
      Nakamura A, Togashi Y, Orime K, Sato K, Shirakawa J, Ohsugi M, Kubota N, Kadowaki T, Terauchi Y
    • Journal Title

      Diabetologia

    • Peer Reviewed
  • [Journal Article] Impact of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance, beta cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet2012

    • Author(s)
      Sato K, Nakamura A, Shirakawa J, Muraoka T, Togashi Y, Shinoda K, Orime K, Kubota N, Kadowaki T, Terauchi Y
    • Journal Title

      Endocrinology

      Volume: 153 Pages: 1093-102

    • Peer Reviewed
  • [Journal Article] Protective effect of a dipeptidyl peptidase-4(DPP-4) inhibitor against increasedβcell apoptosis induced by dietary sucrose and linoleic acid in mice with diabetes2011

    • Author(s)
      Shirakawa J, Amo K, Ohminami H, Orime K, Togashi Y, Ito Y, Tajima K, Koganei M, Sasaki H, Takeda E, Terauchi Y
    • Journal Title

      J Biol Chem

      Volume: 286(29) Pages: 25467-76

    • Peer Reviewed
  • [Journal Article] Impaired in sulin signaling in endo the lial cells reduces in sulin-in duced glucose uptake by skeletal muscle2011

    • Author(s)
      Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, Itoh S, Takamoto I, Sasako T, Kumagai K, Kawai T, Hashimoto S, Kobayashi T, Sato M, Tokuyama K, Nishimura S, Tsunoda M, Ide T, Murakami K, Yamazaki T, Ezaki O, Kawamura K, Masuda H, Moroi M, Sugi K, Oike Y, Shimokawa H, Yanagihara N, Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T
    • Journal Title

      Cell Metab

      Volume: 13 Pages: 294-307

    • Peer Reviewed
  • [Journal Article] Diet-induced adipose tissue in flammation and liver steatosis are prevented by DPP-4 in hibition in diabetic mice2011

    • Author(s)
      Shirakawa J, Fujii H, Ohnuma K, Sato K, Ito Y, Kaji M, Sakamoto E, Koganei M, Sasaki H, Nagashima Y, Amo K, Aoki K, Morimoto C, Takeda E, Terauchi Y
    • Journal Title

      Diabetes

      Volume: 60 Pages: 1246-1257

    • Peer Reviewed
  • [Journal Article] Effect of long-term treatment with a small molecule glucokinase activator on glucose metabolism, lipid profiles, and hepatic function2011

    • Author(s)
      Nakamura A, Hiroko Shimazaki H, Ohyama S, Eiki J, Terauchi Y
    • Journal Title

      J. Diabetes Invest

      Volume: 2 Pages: 276-279

    • Peer Reviewed
  • [Journal Article] Ezetimibe decreases SREBP-1c expression in liver and reverses hepatic insulin resistance in mice fed a high-fat diet2011

    • Author(s)
      Muraoka T, Aoki K, Iwasaki T, Shinoda K, Nakamura A, Aburatani H, Mori S, Tokuyama K, Kubota N, Kadowaki T, Terauchi Y
    • Journal Title

      Metabolism

      Volume: 60 Pages: 617-628

    • Peer Reviewed
  • [Journal Article] Effects of miglitol, sitagliptin or their combination on plasma glucose, insulin and incretin levels in non-diabetic men2010

    • Author(s)
      Aoki K, Masuda K, Miyazaki T, Togashi Y, Terauchi Y
    • Journal Title

      Endocr J

      Volume: 57 Pages: 667-672

    • Peer Reviewed
  • [Journal Article] Decreased insulin secretion and accumulation of triglyceride in.-cells overexpressing a dominant-negative form of AMP-activated protein kinase2010

    • Author(s)
      Okazaki Y, Eto K, Yamashita T, Okamoto M, Ohsugi M, Noda M, Terauchi Y, Kadowaki T
    • Journal Title

      Endocr J

      Volume: 57(2) Pages: 141-152

    • Peer Reviewed
  • [Journal Article] Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease2009

    • Author(s)
      Nozaki Y, Fujita K, Yoneda M, Wada K, Shinohara Y, Takahashi H, Kirikoshi H, Inamori M, Kubota K, Saito S, Mizoue T, Masaki N, Nagashima Y, Terauchi Y, Nakajima A
    • Journal Title

      J. Heaptol

      Volume: 51(3) Pages: 548-56

    • Peer Reviewed
  • [Journal Article] The role of the liver in glucose homeostasis in PI 3-kinase p85.-deficient mice2009

    • Author(s)
      Aoki K, Matsui J, Kubota N, Nakajima H, Iwamoto K, Takamoto I, Tsuji Y, Ohno A, Mori S, Tokuyama K, Murakami K, Asano T, Aizawa S, Tobe K, Kadowaki T, Terauchi Y
    • Journal Title

      Am. J. Physiol. Endocrinol. Metab

      Volume: 296 Pages: 842-853

    • Peer Reviewed
  • [Journal Article] Impact of small molecule glucokinase activator on glucose metabolism,・cell function and mass2009

    • Author(s)
      Nakamura A, Terauchi Y, Ohyama S, Kubota J, Shimazaki H, Nambu T, Takamoto I, Kubota N, Eiki J, Yoshioka N, Kadowaki T, Koike T
    • Journal Title

      Endocrinology

      Volume: 150 Pages: 1147-1154

    • Peer Reviewed
  • [Presentation] The regulation of beta cell ER stress and apoptosis by glucokinase mediated signals2011

    • Author(s)
      Shirakawa J.
    • Organizer
      日本-デンマーク「分子糖尿病学」ワークショップ(招待講演)
    • Place of Presentation
      コペンハーゲン(デンマーク)
    • Year and Date
      2011-10-21
  • [Presentation] Beta Cell Function and Proliferation in Response to Small Molecule Glucokinase Activator under Various Conditions2011

    • Author(s)
      Nakamura A, et al
    • Organizer
      第71回米国糖尿病学会
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2011-06-24
  • [Presentation] Protective effects of glucokinase activator on the onset of diabetes andβcell apoptosis in Akita(Ins2) mice2011

    • Author(s)
      Shirakawa J, et al
    • Organizer
      第71回米国糖尿病学会
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2011-06-24
  • [Presentation] Impact of vildagliptin on glucose tolerance, and beta cell mass in insulin receptor substrate-2-knockout mice2011

    • Author(s)
      Sato K, et al
    • Organizer
      第71回米国糖尿病学会
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2011-06-24
  • [Presentation] Trefoil factor 2(TFF2) induces proliferation of pancreaticβcells2011

    • Author(s)
      Orime K, et al
    • Organizer
      第71回米国糖尿病学会
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2011-06-24
  • [Presentation] βcell proliferation and expansion ofβcell mass were independent of glucokinase in 60% partial pancreatectomized mice2011

    • Author(s)
      Togashi Y, et al
    • Organizer
      第71回米国糖尿病学会
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2011-06-24
  • [Presentation] The role of IRS-2 in the regulation of pancreatic beta cell mass in response to glucokinase activator2011

    • Author(s)
      Nakamura A, et al
    • Organizer
      第54回日本糖尿病学会年次学術集会(招待講演)
    • Place of Presentation
      札幌(日本)
    • Year and Date
      2011-05-19
  • [Presentation] Impact of small molecule glucokinase activator on the regulation of beta cell function and mass under various conditions2011

    • Author(s)
      Terauchi Y.
    • Organizer
      日本-デンマーク「分子糖尿病学」ワークショップ
    • Place of Presentation
      臨床研究情報センター(兵庫)
    • Year and Date
      2011-03-08
  • [Presentation] インクレチン系の機序とその糖尿病治療への応用GLP-1受容体作動薬2011

    • Author(s)
      寺内康夫
    • Organizer
      第45回糖尿病学の進歩
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2011-02-19
  • [Presentation] 糖尿病-最新の進歩2011

    • Author(s)
      寺内康夫
    • Organizer
      第14回日本病態栄養学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)(招待講演)
    • Year and Date
      2011-01-16
  • [Presentation] Protective effects of DPP-4 inhibitor against increasedβcell apoptosis with multiorgan glucolipotoxicity by a combination of dietary sugar and fatty acid2010

    • Author(s)
      Shirakawa J, et al
    • Organizer
      第46回欧州糖尿病学会
    • Place of Presentation
      ストックホルム(スウェーデン)
    • Year and Date
      2010-09-21
  • [Presentation] Proliferation of Beta Cells Stimulated by Small Molecule Glucokinase Activator2010

    • Author(s)
      Nakamura A, et al
    • Organizer
      第70回米国糖尿病学会
    • Place of Presentation
      オーランド(米国)
    • Year and Date
      2010-06-25
  • [Presentation] Increasedβcell apoptosis with multiorgan glucolipotoxicity by a combination of dietary sugar and fatty acid and protective effects of DPP-4 inhibitor des-fluoro-sitagliptin against them2010

    • Author(s)
      Shirakawa J, et al
    • Organizer
      第70回米国糖尿病学会
    • Place of Presentation
      オーランド(米国)
    • Year and Date
      2010-06-25
  • [Presentation] 食事摂取により誘導される多臓器におけるglucolipotoxicityに対するDPP-4阻害薬des-fluoro-sitagliptinによる抑制効果2010

    • Author(s)
      白川純, 他
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山コンベンションセンター(岡山)
    • Year and Date
      2010-05-27
  • [Presentation] β細胞の発生から細胞死The role of glucokinase in the regulation of beta cell proliferation2010

    • Author(s)
      中村昭伸、寺内康夫
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山コンベンションセンター(岡山)
    • Year and Date
      2010-05-27
  • [Presentation] グルコキナーゼ活性化薬の膵β細胞増殖作用におけるIRS-2の役割2010

    • Author(s)
      中村昭伸, 他
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山コンベンションセンター(岡山)
    • Year and Date
      2010-05-27
  • [Presentation] グルコキナーゼ活性化薬の膵β細胞増殖作用の分子機構2010

    • Author(s)
      中村昭伸, 他
    • Organizer
      第47回日本臨床分子医学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Year and Date
      2010-04-11
  • [Presentation] Roles of glucose metabolism and insulin signaling inβcell function and mass2010

    • Author(s)
      寺内康夫
    • Organizer
      デンマーク「分子糖尿病学」ワークショップ
    • Place of Presentation
      コペンハーゲン
    • Year and Date
      2010-03-23
  • [Presentation] 薬物治療の選択と治療の進め方2010

    • Author(s)
      寺内康夫
    • Organizer
      糖尿病学の進歩
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-06
  • [Presentation] グルコキナーゼ活性化薬による膵β細胞増殖メカニズムの解析2010

    • Author(s)
      中村昭伸
    • Organizer
      日本糖尿病・肥満動物学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-01-22
  • [Presentation] 食事摂取により誘導される多臓器のglucolipo toxicityに対するDPP-4阻害薬des-fluoro-sitagliptinによる改善効果2010

    • Author(s)
      白川純
    • Organizer
      日本糖尿病・肥満動物学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-01-22
  • [Presentation] 2型糖尿病における膵β細胞異常(機能・量)2009

    • Author(s)
      寺内康夫
    • Organizer
      日本糖尿病学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-22
  • [Presentation] グルコキナーゼ依存性・非依存性膵β細胞量調節機構の解明と膵β細胞量増加法の開発2009

    • Author(s)
      中村昭伸
    • Organizer
      日本内分泌学会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-23
  • [Book] 2型糖尿病の薬物療法ハンドブック2011

    • Author(s)
      寺内康夫
    • Total Pages
      170
    • Publisher
      南江堂
  • [Book] Principles and Practice内分泌・代謝2011

    • Author(s)
      寺内康夫、鯉渕則之、後藤英司
    • Total Pages
      343
    • Publisher
      文光堂
  • [Book] EBM糖尿病ハンドブック2010

    • Author(s)
      寺内康夫
    • Total Pages
      544
    • Publisher
      中外医学社
  • [Remarks]

    • URL

      http://www-user.yokohama-cu.ac.jp/~nai3naib/

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Published: 2013-07-31   Modified: 2013-08-08  

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