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IRS1/insulin signaling-induced repair mechanisms of podocyte injury

Research Project

Project/Area Number 26461230
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKindai University

Principal Investigator

MIMA Akira  近畿大学, 医学部附属病院, 講師 (00432401)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsインスリンシグナル / ポドサイトアポトーシス / IRS1 / 糖尿病性腎症 / インスリン受容体基質
Outline of Final Research Achievements

Immunoblot analyses showed insulin (10nM) increased the levels of phosphorylation of Akt (pAkt) which had anti-apoptotic effects by 4.5±0.7-fold. In contrast, high glucose (HG; 20mM) levels decreased the expression by 7.8%. Insulin increased tyrosine phosphorylation of insulin substrate (IRS)1 by 2-fold in low glucose (LG; 5.6mM), while HG decreased the expression by 10%. Infection with IRS1 using adenoviral vector (Ad-IRS1) decreased HG-induced podocyte apoptosis by 57%. To assess the role of IRS1 in mediating the podocyte apoptosis, IRS1 expression was reduced with siIRS1. Knockdown of IRS1 in podocytes increased apoptosis by 2.4±0.4-fold. Lastly, DPP-4 inhibitor increased the levels of pAkt by 131±28%. These results suggest that increases in insulin signaling activity in podocytes using Ad-IRS1 or DPP-4i could inhibit HG-induced podocyte apoptosis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (23 results)

All 2017 2016 2015 2013

All Journal Article (14 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 4 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Efficacy of mizoribine and prednisolone combination therapy in adult patients with IgA vasculitis2017

    • Author(s)
      Mima A
    • Journal Title

      Rheumatol Int

      Volume: 印刷中 Issue: 8 Pages: 1387-1393

    • DOI

      10.1007/s00296-017-3685-6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Methotrexate induced pneumatosis intestinalis under hemodialysis patient2017

    • Author(s)
      Mima A, Nagahara D, Tansho K
    • Journal Title

      Hemodial Int

      Volume: 21 Issue: 1

    • DOI

      10.1111/hdi.12459

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Inflammatory Regulation in Diabetes and Metabolic Dysfunction2017

    • Author(s)
      Zhong J, Gong Q, Mima A
    • Journal Title

      J Diabetes Res

      Volume: ー Pages: 5165268-5165268

    • DOI

      10.1155/2017/5165268

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive Glomerulonephritis2016

    • Author(s)
      Araki M, Matsubara T, Abe H, Torikoshi K, Mima A, Iehara N, Fukatsu A, Kita T, Arai H, Doi T
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 31216-31216

    • DOI

      10.1038/srep31216

    • NAID

      120006345067

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance2016

    • Author(s)
      Katagiri S, Park K, Maeda Y, Rao TN, Khamaisi M, Li Q, Yokomizo H, Mima A, Lancerotto L, Wagers A, Orgill DP, King GL
    • Journal Title

      Diabetes

      Volume: 65 Issue: 9 Pages: 2760-2771

    • DOI

      10.2337/db15-1721

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Insulin decreases atherosclerosis by inducing endothelin receptor B expression2016

    • Author(s)
      Park K, Mima A, Li Q, Rask-Madsen C, He P, Mizutani K, Katagiri S, Maeda Y, Wu IH, Khamaisi M, Preil SR, Maddaloni E, Sorensen D, Rasmussen LM, Huang PL, King GL
    • Journal Title

      JCI Insight

      Volume: 1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tocilizumab Resistant Nephrotic Syndrome and Protein Losing Gastroeneropathy Due to Amyloidosis in Chronic Kidney Disease2016

    • Author(s)
      Mima A
    • Journal Title

      West Indian Med J

      Volume: 印刷中

    • DOI

      10.7727/wimj.2016.202

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Incretin-Based Therapy for Prevention of Diabetic Vascular Complications2016

    • Author(s)
      Mima A
    • Journal Title

      J Diabetes Res

      Volume: ー Pages: 1379274-1379274

    • DOI

      10.1155/2016/1379274

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] LCAPの返血時に返血側を加温することで鋭い血管痛が消失した1症例2016

    • Author(s)
      左官 真以子, 川崎 広樹, 西辻 冬馬, 津川 真伍, 高儀 良平, 末野 優史, 小山 和彦, 植田 隆介, 堀 辰之, 小木 幸人, 丹正 幸佑, 長原 大, 美馬 晶
    • Journal Title

      日本アフェレシス学会雑誌

      Volume: 35 Pages: 179-179

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 奈良県における慢性透析患者の現況 2014年12月末の統計的観察2016

    • Author(s)
      米田 龍生, 吉田 克法, 平尾 佳彦, 斎藤 能彦, 柏井 浩希, 丘田 英人, 三馬 省二, 熊本 廣実, 青山 秀雄, 松原 博, 松本 宗輔, 金子 佳照, 吉岡 伸夫, 枝川 光太郎, 枝川 篤永, 森田 壮平, 阿部 泰志, 松田 尚史, 田中 正己, 美馬 晶
    • Journal Title

      奈良県医師会透析部会誌

      Volume: 21 Pages: 21-27

    • NAID

      40020982222

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Bone Morphogenetic Protein 4 and Smad1 Mediate Extracellular Matrix Production in the Development of Diabetic Nephropathy.2015

    • Author(s)
      Matsubara T, Araki M, Abe H, Ueda O, Jishage K, Mima A, Goto C, Tominaga T, Kinosaki M, Kishi S, Nagai K, Iehara N, Fukushima N, Kita T, Arai H, Doi T.
    • Journal Title

      Diabetes

      Volume: 64 Issue: 8 Pages: 2978-2990

    • DOI

      10.2337/db14-0893

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 血管内皮細胞内インスリンシグナルを用いた劣化腹膜治療法の開発2015

    • Author(s)
      美馬 晶
    • Journal Title

      日本透析医会雑誌

      Volume: 30 Pages: 158-160

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] CKD診断マーカーとしての尿中Smad1の評価2015

    • Author(s)
      美馬 晶、松浦 元一、土井 俊夫
    • Journal Title

      腎臓

      Volume: 37 Pages: 32-36

    • Related Report
      2014 Research-status Report
  • [Journal Article] Inflammation and oxidative stress in diabetic nephropathy : new insights on its inhibition as new therapeutic targets2013

    • Author(s)
      Mima A
    • Journal Title

      J Diabetes Res

      Volume: 該当なし Pages: 207140-207140

    • DOI

      10.1155/2014/207140

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] IgGλ型軽鎖沈着症による二次性膜性増殖性糸球体腎炎に対し、レナリドミドが腎機能障害を改善した一例2016

    • Author(s)
      長原 大、丹正 幸佑、美馬 晶
    • Organizer
      第46回日本腎臓学会西部学術大会
    • Place of Presentation
      シーガイアコンベンションセンター(宮崎市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血液透析患者に対するメトトレキセート投与により壊死性腸管気腫症を引き起こした1例2016

    • Author(s)
      長原 大、丹正 幸佑、美馬 晶
    • Organizer
      第61回日本透析医学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ホーチミン透析医学会(HSDT)設立報告と今後の課題2016

    • Author(s)
      松原 弘和、兵藤 透、小久保 謙一、花房 規男、美馬 晶、瀧澤 亜由美、若井 陽希、Nguyen Duc Nam、川村 明夫
    • Organizer
      第61回日本透析医学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ベトナムにおける透析医療の現状調査~ベトナム南部最大の総合病院での調査~2016

    • Author(s)
      瀧澤 亜由美、小久保 謙一、花房 規男、美馬 晶、松原 弘和、兵藤 透、石森 勇、村上 淳、金子 岩和、峰島 三千男、土谷 健、新田 孝作、秋葉 隆
    • Organizer
      第61回日本透析医学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hemodialysis Vascular Access Complications2015

    • Author(s)
      Akira Mima
    • Organizer
      Launching Ceremony and the Scientific Congress of Ho Chi Minh City Society of Dialysis Therapies (HSDT), the CME Course on Nephrology and Dialysis, and the 1st Congress of the HSDT
    • Place of Presentation
      ベトナム、ホーチミン
    • Year and Date
      2015-12-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The effects of linagliptin on insulin signaling and apoptosis of the podocytes in diabetic nephropathy2015

    • Author(s)
      Akira Mima, Toshinori Yasuzawa, Shigeru Ueshima, Kazuo Tsubaki
    • Organizer
      International Diabetes Federation World Diabetes Congress 2015
    • Place of Presentation
      カナダ、バンクーバー
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 難治性特発性血小板減少症を合併した維持透析患者に対しトロンボポエチン受容体作動薬が有効であった一例2015

    • Author(s)
      藤田茉莉子、美馬 晶、椿 和央
    • Organizer
      第60回日本透析医学会学術集会・総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Augmenting Endothelial Cell Insulin Signaling Prevents Accelerated Intestinal Tumor Formation in Obesity2015

    • Author(s)
      XUANCHUN WANG, DITTE SØRENSEN, SAMUEL LOCKHART, QIAN LI, KYOUNGMIN PARK, AKIRA MIMA, LARS M. RASMUSSEN, GEORGE L. KING, CHRISTIAN RASK-MADSEN
    • Organizer
      75th American Diabetes Association Scientific Sessions
    • Place of Presentation
      アメリカ、ボストン
    • Year and Date
      2015-06-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] GLP-1受容体作動薬の腎保護作用とその分子機構(2)2015

    • Author(s)
      美馬 晶
    • Organizer
      第一回日本慢性疾患重症化予防学会
    • Place of Presentation
      兵庫県西宮市
    • Year and Date
      2015-02-15
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2020-01-20  

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