• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Tissue Engineered Islets derived from glucosensitive Beta cells

Research Project

Project/Area Number 20K08972
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionFukuoka University

Principal Investigator

Kodama Shohta  福岡大学, 医学部, 教授 (90549338)

Co-Investigator(Kenkyū-buntansha) 田中 智子  福岡大学, 医学部, 講師 (10380528)
坂田 直昭  福岡大学, 医学部, 准教授 (50431565)
吉松 軍平  福岡大学, 医学部, 准教授 (50569275)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsグルコセンサー / 膵β細胞 / 高感度血糖応答性 / グアニル酸結合タンパク / GPCR / MIP-GFP Tg / Glucose Uptake kit / 組織工学的膵島 / GLUT2 / Glucose Uptake Probe / RNAseq / アノテーション解析 / Ca inflex / Fura-2AM 標識 / 血糖高感度β細胞 / 膵島 / GCaMP2 / 組織工学
Outline of Research at the Start

MIP-GFPマウス膵島から単細胞化したβ細胞を用いた、Fura-2AM で標識された Ca2+の取り込み実験では、一連のCa2+の流入の動態から、GULT2より取り込まれたGlucoseの反応系を捉えることが可能である。さらに標識されたCa2+の取り込みを恒常的に追視する事により、グルコース応答に均一性や相同性を維持してない、β細胞を中等度高血糖反応型β細胞と高度高血糖反応型β細胞としてソーティング選別し解析を行うことが可能である。さらに、その反応性の根幹に結びつくグルコセンサーの同定に、クラスター解析の手法で RNA sequence を行うことに着想し、血糖高感度型膵島の創出を目指す。

Outline of Final Research Achievements

MIP-GFP islets were prepared for single cells then the cells were sorted by fluorescent intensity based on GFP. The population of sorted cells were separated by four groups, GFP negative, GFP dim, GFP mid and GFP high. The GFP high population indicated the highest expression of Ins2 using qPCR as Beta cells.
Glucose probe was also used to distinguish for glucose uptake between high and low. The populations were identified between glucose uptake strong positive with GFP mid and glucose uptake low positive with GFP high. To investigate for glucose sensors, Annotation analysis, DAVID was performed. At the result of analysis, glucose uptake strong positive group was expressed higher than glucose uptake low positive group, specially in guanylate-binding proteins and G-protein coupled receptor.

Academic Significance and Societal Importance of the Research Achievements

膵島細胞はBeta細胞をはじめ様々な種類の内分泌細胞を包括していることが知られている。またインスリンを分泌する膵Beta細胞は均一の細胞集団から構成されていると信じられていた。ところがBeta細胞にはインスリン分泌に関して指令塔となるハブ細胞が存在することが明らかとなっている。しかしながら、この伝達経路のみでインスリン分泌調節機構の全てを包括していない。そこで個々の膵Beta細胞にエピゲネチックな背景によりインスリン分泌に差異が生じると仮定し、グルコースの取り込み差異によるグルコセンサー関連遺伝子を同定した。今後、高感度なBeta細胞を組織工学的に編成し、細胞移植や創薬に展開可能となっている。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (35 results)

All 2023 2022 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (26 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Journal Article] Induction of potassium channel regulator KCNE4 in a submandibular lymph node metastasis model2022

    • Author(s)
      Mano Ryosuke、Tanaka Tomoko、Hashiguchi Shiho、Takahashi Hiroyuki、Sakata Naoaki、Kondo Seiji、Kodama Shohta
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 13208-13208

    • DOI

      10.1038/s41598-022-15926-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of NR5A1 Phosphorylation Alleviates a Transcriptional Suppression Defect Caused by a Novel <i>NR0B1</i> Mutation2022

    • Author(s)
      Abe Ichiro、Tanaka Tomoko、Ohe Kenji、Fujii Hideyuki、Nagata Mai、Ochi Kentaro、Senda Yuki、Takeshita Kaori、Koga Midori、Kudo Tadachika、Enjoji Munechika、Yanase Toshihiko、Kobayashi Kunihisa
    • Journal Title

      Journal of the Endocrine Society

      Volume: 6 Issue: 6

    • DOI

      10.1210/jendso/bvac068

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis.2021

    • Author(s)
      H, Sakata N, Nishimura M, Tanaka T, Shimizu M, Yoshimatsu G, Kawakami R, Wada H, Sawamoto O, Matsumoto S, Kodama S.
    • Journal Title

      Xenotransplantation

      Volume: - Issue: 4

    • DOI

      10.1111/xen.12693

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lymphangiogenesis and angiogenesis rescue murine ischemic hindlimb via transient receptor potential vanilloid 42021

    • Author(s)
      Yamada H, Sakata N, Tanaka T, Tagashira H, Yoshimatsu G, Kawakami R, Wada H, Iwamoto T, Kodama S
    • Journal Title

      Journal of Pharmacological Science

      Volume: - Issue: 4 Pages: 244-248

    • DOI

      10.1016/j.jphs.2021.04.009

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of NLRP3 inflammasome by MCC950 improves the metabolic outcome of islet transplantation by suppressing IL-1β and islet cellular death2020

    • Author(s)
      Matsuoka Taisuke、Yoshimatsu Gumpei、Sakata Naoaki、Kawakami Ryo、Tanaka Tomoko、Yamada Teppei、Yoshida Yoichiro、Hasegawa Suguru、Kodama Shohta
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17920-17920

    • DOI

      10.1038/s41598-020-74786-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanism of Transplanted Islet Engraftment in Visceral White Adipose Tissue2020

    • Author(s)
      Sakata Naoaki、Yoshimatsu Gumpei、Tanaka Tomoko、Yamada Teppei、Kawakami Ryo、Kodama Shohta
    • Journal Title

      Transplantation

      Volume: 104 Issue: 12 Pages: 2516-2527

    • DOI

      10.1097/tp.0000000000003400

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] White Adipose Tissue as a Site for Islet Transplantation2020

    • Author(s)
      Sakata Naoaki、Yoshimatsu Gumpei、Kodama Shohta
    • Journal Title

      Transplantology

      Volume: 1 Issue: 2 Pages: 55-70

    • DOI

      10.3390/transplantology1020006

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Roles of Collagen in Islet Transplantation2020

    • Author(s)
      Sakata Naoaki、Yoshimatsu Gumpei、Kodama Shohta
    • Journal Title

      OBM Transplantation

      Volume: 4 Issue: 4

    • DOI

      10.21926/obm.transplant.2004127

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Outcomes of Islet Autotransplantation in Chronic Pancreatitis Patients with Complete Acinar Atrophy.2020

    • Author(s)
      Yoshimatsu G , Kanak MA, Vasu S, Kumano K, Lawrence M, Onaca N, Takita M, Levy MF, Naziruddin B.
    • Journal Title

      Cell Tranaplantation

      Volume: 29 Pages: 096368972094924-096368972094924

    • DOI

      10.1177/0963689720949242

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ブタ膵島異種移植の実現に向けて-ブタ膵島長期培養の可能性-2023

    • Author(s)
      坂田直昭
    • Organizer
      第50回日本膵・膵島移植学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 長期培養がブタ膵島に与える特性・機能面への影響の検証2023

    • Author(s)
      坂田直昭
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 異種移植の今後の展望について-膵島移植への転用について-2022

    • Author(s)
      小玉正太
    • Organizer
      第40回九州実験動物研究会総会・第42回日本実験動物技術者協会九州支部研究発表会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Availability of using amnion for islet transplantation2022

    • Author(s)
      坂田直昭
    • Organizer
      International Congress of The Transplantation Society (TTS 2022)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ブタ膵島分離における“switch”の意義2022

    • Author(s)
      坂田直昭
    • Organizer
      第20回日本組織移植学会総会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ブタ膵島異種移植の実現に向けて2022

    • Author(s)
      坂田直昭
    • Organizer
      第58回日本移植学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 膵島移植における今後の適応について2022

    • Author(s)
      吉松軍平
    • Organizer
      第58回 日本移植学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Current issue of islet transplantation for insulin independent diabetes mellitus with severe hypoglycemic event2022

    • Author(s)
      吉松軍平
    • Organizer
      The 34th meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery
    • Related Report
      2022 Annual Research Report
  • [Presentation] Implantation of Steroidogenic Cells Derived from Human Adipose-derived Stem Cells Extends Survival in a Mouse Model of Adrenal Insufficiency2022

    • Author(s)
      田中智子
    • Organizer
      ENDO2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MIN6細胞においてスプライシング操作薬が誘導するPax6スプライシングバリアント2022

    • Author(s)
      田中智子
    • Organizer
      第95回日本内分泌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] “Bioartificial islets, composed by alginate-poly-L-ornithine-alginate (APA), three layered microencapsulated neonatal porcine islets (NPIs) - Is it a realistic option to supply as clinical islet xenotransplantation (xenoTx) ?“2021

    • Author(s)
      Shohta Kodama
    • Organizer
      The 2nd Congress of Asian Pancreas and Islet Transplant Association
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 保険診療のもとでの膵島移植の現状と未来2021

    • Author(s)
      小玉正太
    • Organizer
      第48回日本膵・膵島移植研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] 異種移植の新規展開と臓器再生2021

    • Author(s)
      小玉正太
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脂肪被覆膵島移植とその手法2021

    • Author(s)
      坂田直昭
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] The protocol of fat-covered islet transplantation using epididymal white adipose tissue2021

    • Author(s)
      Naoaki Sakata
    • Organizer
      The 2nd Congress of Asian Pancreas and Islet Transplant Association
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 臨床異種膵島移植実現のためのマイクロミニブタを使用した膵島単離と回収膵島の機能評価2021

    • Author(s)
      坂田直昭
    • Organizer
      第23回日本異種移植研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] NR5A1誘導性ステロイド産生細胞の移植による副腎不全モデルのレスキュー2021

    • Author(s)
      田中智子
    • Organizer
      第20回日本再生医療学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 膵臓移植における糖尿病内科医と移植外科医との連携2021

    • Author(s)
      吉松軍平
    • Organizer
      第48回日本膵・膵島移植研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] Laparoscopic complete mesocolic excision and central vascular ligation for right hemicolectomy2021

    • Author(s)
      吉松軍平
    • Organizer
      第33回日本内視鏡外科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 膵島細胞研究の新たな展開2020

    • Author(s)
      小玉正太
    • Organizer
      第58回日本糖尿病学会九州地方会
    • Related Report
      2020 Research-status Report
  • [Presentation] The Mechanism How the Transplanted Islets Engraft Into White Adipose Tissue2020

    • Author(s)
      Naoaki Sakata
    • Organizer
      2020 American Transplant Congress
    • Related Report
      2020 Research-status Report
  • [Presentation] The advanced mechanisms of islet-engraftment onto white adipose tissue2020

    • Author(s)
      Naoaki Sakata
    • Organizer
      TTS2020
    • Related Report
      2020 Research-status Report
  • [Presentation] 副腎皮質癌の新規治療標的としてのNR5A1の複数エキソン除外制御機構2020

    • Author(s)
      田中智子
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] NR5A1 RNAのスプライシング調節を介したNR5A1発現抑制:各種薬剤の検討2020

    • Author(s)
      田中智子
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 膵の硬度からみた膵全摘自家膵島移植の適応について2020

    • Author(s)
      吉松軍平
    • Organizer
      第56回 日本移植学会オンライン総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Inhibiting NLRP3 inflammasome ameliorates glucose fluctuation through reducing apoptosis and infiltration of inflammatory cells after intraportal islet transplantation in rodent model2020

    • Author(s)
      吉松軍平
    • Organizer
      American Transplant Congress
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi