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Abnormality of O-GlcNAcylation and pathogenesis of beta cell dysfunction

Research Project

Project/Area Number 15K09383
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionShiga University of Medical Science

Principal Investigator

SEKINE OSAMU  滋賀医科大学, 医学部, 助教 (00402719)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsO-GlcNAc修飾 / 膵β細胞 / インスリン分泌 / 糖尿病 / O-結合型糖修飾 / 膵臓
Outline of Final Research Achievements

O-GlcNAcylation is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) as the post-translational modification and serves in sensing intracellular nutrients by modulating various cellular process. Abnormality of O-GlcNAcylation may be associated with the pathogenesis of metabolic disease such as diabetes mellitus. We investigated insulin secretion and pancreatic beta cell function using tamoxifen-inducible pancreatic beta cell-specific Ogt-KO mice. These mice displayed transient hypoglycemia associated with higher insulin secretion and accelerated adiposity (early phase), followed by subsequent hyperglycemia with insulin depletion accompanied by beta cell apoptosis (late phase). In addition, tamoxifen-inducible global Ogt-KO mice exhibited a lethal phenotype from 4 weesks post injection. These findings suggest that O-GlcNAcylation plays a crucial role in pancreatic beta cell function and survival under physiological conditions.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (22 results)

All 2018 2017 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Int'l Joint Research: 3 results) Book (7 results)

  • [Journal Article] Lack of O-GlcNAcylation enhances exercise-dependent glucose utilization potentially through AMP-activated protein kinase activation in skeletal muscle2018

    • Author(s)
      Murata Koichiro、Morino Katsutaro、Ida Shogo、Ohashi Natsuko、Lemecha Mengistu、Park Shi-Young、Ishikado Atsushi、Kume Shinji、Choi Cheol Soo、Sekine Osamu、Ugi Satoshi、Maegawa Hiroshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 2 Pages: 2098-2104

    • DOI

      10.1016/j.bbrc.2017.12.081

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diverse metabolic effects of O-GlcNAcylation in the pancreas but limited effects in insulin-sensitive organs in mice2017

    • Author(s)
      Ida Shogo、Morino Katsutaro、Sekine Osamu、Ohashi Natsuko、Kume Shinji、Chano Tokuhiro、Iwasaki Kanako、Harada Norio、Inagaki Nobuya、Ugi Satoshi、Maegawa Hiroshi
    • Journal Title

      Diabetologia

      Volume: 60 Issue: 9 Pages: 1761-1769

    • DOI

      10.1007/s00125-017-4327-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pivotal Role of O -GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis2017

    • Author(s)
      Ohashi Natsuko、Morino Katsutaro、Ida Shogo、Sekine Osamu、Lemecha Mengistu、Kume Shinji、Park Shi-Young、Choi Cheol Soo、Ugi Satoshi、Maegawa Hiroshi
    • Journal Title

      Diabetes

      Volume: 66 Issue: 9 Pages: 2351-2362

    • DOI

      10.2337/db16-1427

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] O-GlcNAcylation plays a physiologically important role in glucose homeostasis in pancreatic β cells rather than in insulin target tissues2017

    • Author(s)
      Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
    • Journal Title

      Diabetologia (in press)

      Volume: -

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] O-linked β-N-acetylglucosamine modification of proteins is essential for foot process maturation and survival in podocytes.2017

    • Author(s)
      Ono S, Kume S, Yasuda-Yamahara M, Yamahara K, Takeda N, Chin-Kanasaki M, Araki H, Sekine O, Yokoi H, Mukoyama M, Uzu T, Araki SI, Maegawa H.
    • Journal Title

      Nephrol Dial Transplant.

      Volume: 未定 Issue: 9 Pages: 000-000

    • DOI

      10.1093/ndt/gfw463

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal.2015

    • Author(s)
      Nagayama K, Morino K, Sekine O, Nakagawa F, Ishikado A, Iwasaki H, Okada T, Tawa M, Sato D, Imamura T, Nishio Y, Ugi S, Kashiwagi A, Okamura T, Maegawa H
    • Journal Title

      Nutrients

      Volume: 7(9) Issue: 9 Pages: 8112-8126

    • DOI

      10.3390/nu7095381

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sonoda N, Morimoto A, Ugi S, Morino K, Sekine O, Nemoto K, Godai K, Maegawa H, Miyamatsu N. Predictors for Mild and Severe Hypoglycemia in Insulin-Treated Japanese Diabetic Patients.2015

    • Author(s)
      Sonoda N, Morimoto A, Ugi S, Morino K, Sekine O, Nemoto K, Godai K, Maegawa H, Miyamatsu N
    • Journal Title

      PLoS One

      Volume: 10(6) Issue: 6 Pages: e0130584-e0130584

    • DOI

      10.1371/journal.pone.0130584

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Comprehensive Analysis to Reveal Physiological Role of O-GlcNAcylation in Glucose Metabolism by Using Tissue-Specific Ogt Knockout Mice2017

    • Author(s)
      SHOGO IDA, KATSUTARO MORINO, OSAMU SEKINE, NATSUKO OHASHI, SHINJI KUME, KANAKO IWASAKI, NORIO HARADA, NOBUYA INAGAKI, SATOSHI UGI, HIROSHI MAEGAWA
    • Organizer
      American Diabetes Association 77th
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lack of O-GlcNAcylation Enhances Exercise-Dependent Glucose Utilization through Amp Kinase Activation in Skeletal Muscle2017

    • Author(s)
      KOICHIRO MURATA, KATSUTARO MORINO, SHOGO IDA, NATSUKO OHASHI, HIROTAKA IWASAKI, MENGISTU LEMECHA SHUKARE, OSAMU SEKINE, SHINJI KUME, SHI YOUNG PARK, CHEOL SOO CHOI, SATOSHI UGI, HIROSHI MAEGAWA
    • Organizer
      American Diabetes Association 77th
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic Switch by O-GlcNAcylation Is Essential for Cold-Induced Thermogenesis in Brown Adipose Tissue2017

    • Author(s)
      NATSUKO OHASHI, KATSUTARO MORINO, SHOGO IDA, OSAMU SEKINE, MENGISTU LEMECHA, SHINJI KUME, SHE YOUNG PARK, CHEOL SOO CHOI, SATOSHI UGI, HIROSHI MAEGAWA
    • Organizer
      American Diabetes Association 77th
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵β細胞のO-GlcNAc修飾はインスリン分泌とβ細胞の恒常性維持に重要である2017

    • Author(s)
      井田 昌吾、森野勝太郎、大橋夏子、久米真司、関根 理、岩崎可南子、原田範雄、稲垣暢也、卯木 智、前川 聡
    • Organizer
      日本糖尿病学会年次学術集会 第60回
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨格筋におけるO-GlcNAc修飾の低下はAMPK活性化を介して糖利用の亢進をもたらす2017

    • Author(s)
      村田 幸一郎、森野勝太郎、井田昌吾、大橋夏子、岩﨑広高、Mengistu Lemecha Shukare、関根 理、久米真司、卯木 智、前川 聡
    • Organizer
      日本糖尿病学会年次学術集会 第60回
    • Related Report
      2017 Annual Research Report
  • [Presentation] 褐色脂肪組織のO-GlcNAc修飾は寒冷環境における熱産生に重要である2017

    • Author(s)
      大橋夏子、森野勝太郎、井田昌吾、関根 理、Mengistu Lemecha, 久米真司、Shi-Young Park、Cheol Soo Choi、卯木 智、前川 聡
    • Organizer
      日本糖尿病学会年次学術集会 第60回
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵島特異的Ogt欠損マウスは二相性の血糖・インスリン分泌変化をきたす2016

    • Author(s)
      井田昌吾、関根理、他
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 糖代謝関連臓器におけるO-GlcNAc修飾の網羅的機能解析2015

    • Author(s)
      井田昌吾、関根理、他
    • Organizer
      第58回日本糖尿病学会年次学術集会 若手研究奨励賞
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Book] 医薬ジャーナル 糖尿病の最新治療と総合戦略 SGLT2阻害薬2017

    • Author(s)
      関根 理、前川 聡
    • Total Pages
      7
    • Publisher
      医薬ジャーナル社
    • Related Report
      2017 Annual Research Report
  • [Book] 月刊糖尿病 今、明かされたSGLT2阻害薬の多面的作用と適正使用 SGLT2阻害薬に期待される臨床効果2017

    • Author(s)
      関根 理、前川 聡
    • Total Pages
      12
    • Publisher
      医学出版
    • Related Report
      2017 Annual Research Report
  • [Book] 最新医学 別冊新ABC117「糖尿病」 糖尿病大血管症を伴う血糖管理2016

    • Author(s)
      関根 理、前川 聡
    • Total Pages
      10
    • Publisher
      最新医学社
    • Related Report
      2016 Research-status Report
  • [Book] 新時代の臨床糖尿病学(上) 糖尿病新薬2016

    • Author(s)
      関根 理、前川 聡
    • Total Pages
      3
    • Publisher
      日本臨牀社
    • Related Report
      2015 Research-status Report
  • [Book] 糖尿病 最新の治療 2016-2018 糖尿病ケトアシドーシス2016

    • Author(s)
      関根 理、前川 聡
    • Total Pages
      3
    • Publisher
      南江堂
    • Related Report
      2015 Research-status Report
  • [Book] 糖尿病ケア 2016年春期増刊 魔法の糖尿病患者説目シート+α 糖尿病だと何が悪いの?2016

    • Author(s)
      関根 理、前川 聡
    • Total Pages
      3
    • Publisher
      メディカ出版
    • Related Report
      2015 Research-status Report
  • [Book] ヴィジュアル 糖尿病臨床のすべて インクレチンの膵外作用(改訂板)2015

    • Author(s)
      関根 理、前川 聡
    • Total Pages
      3
    • Publisher
      中山書店
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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