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

Molecular mechanisms of pancreatic beta cell proliferarion via endoplasmic reticulum stress responses

Research Project

Project/Area Number 22K16411
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKyoto University

Principal Investigator

Murakami Takaaki  京都大学, 医学研究科, 助教 (50904017)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords糖尿病 / 小胞体ストレス / 膵β細胞
Outline of Research at the Start

成体の膵β細胞増殖におけるATF6を中心とした小胞体ストレス応答関連因子の役割を解明するとともに、生体膵β細胞量に与えうる影響を検討する。単一細胞RNAシークエンス解析データを基に、膵β細胞特異的KOマウスを用い、膵β細胞増殖誘導モデルである膵部分切除、及び、インスリン受容体ブロッカー投与における成体での膵β細胞増殖への影響を解析することで、複数モデルに共通する、小胞体ストレス応答を介した成体の膵β細胞増殖誘導分子機構を解明する。また、膵β細胞特異的KOマウスの膵β細胞量変化を縦断的に評価し、ATF6を介する小胞体ストレス応答経路が最終的な生体膵β細胞量に与える影響とその分子機構を解明する。

Outline of Final Research Achievements

The purpose of this study is to elucidate the role of ER stress response-related factors, mainly ATF6, in pancreatic β-cell proliferation and its possible effects on the amount of living pancreatic β-cells. Although activation of ATF6 and increase of BrdU-positive cells have been reported in isolated islets cultured under high concentration glucose conditions as well as partial pancreatectomy, few islet-specific analyses of pancreatic β-cells have been conducted, and it was necessary to use a pancreatic β-cell-specific experimental system to clarify the role of ATF6 in inducing pancreatic β-cell proliferation Therefore, it was necessary to use a pancreatic beta cell-specific experimental system to elucidate the role of ATF6 in inducing pancreatic beta cell proliferation. The applicant created a pancreatic β-cell-specific ATF6α knockout mouse based on pancreatic β-cell single cell RNA sequencing data.

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は、膵β細胞増殖におけるATF6を中心としたERストレス応答関連因子の役割を解明するとともに、生体膵β細胞量に与えうる影響とその分子機構を解明することである。本研究では、単一細胞RNAシークエンス解析データを基に、膵β細胞特異的ATF6α欠損マウスを作製した。このマウスを用いた膵β細胞量や膵β細胞増殖能の詳細な解析により、ATF6などERストレス応答経路を標的とし成体膵β細胞増殖を介した膵β細胞量保護効果を有する糖尿病治療の予防・治療法の創出に繋がる新規研究基盤構築への貢献が期待できる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (7 results)

All 2024 2023 2022

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results)

  • [Journal Article] Impact of Prevascularization on Immunological Environment and Early Engraftment in Subcutaneous Islet Transplantation2024

    • Author(s)
      Inoguchi Kenta、Anazawa Takayuki、Fujimoto Nanae、Tada Seiichiro、Yamane Kei、Emoto Norio、Izuwa Aya、Su Hang、Fujimoto Hiroyuki、Murakami Takaaki、Nagai Kazuyuki、Hatano Etsuro
    • Journal Title

      Transplantation

      Volume: -

    • DOI

      10.1097/tp.0000000000004909

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 18F-labeled PEGylated exendin-4 imaging noninvasively differentiates insulinoma from an accessory spleen: the first case report of [18F]FB(ePEG12)12-exendin-4 positron emission tomography/computed tomography for insulinoma2023

    • Author(s)
      Sakaki Kentaro、Murakami Takaaki、Fujimoto Hiroyuki、Shimizu Yoichi、Miyake Kanae Kawai、Otani Daisuke、Kiyobayashi Sakura、Okada Takuya、Fujimoto Masakazu、Hakata Takuro、Yamauchi Ichiro、Shimada Kotaro、Shimizu Hironori、Nagai Kazuyuki、Nakamoto Yuji、Inagaki Nobuya
    • Journal Title

      Frontiers in Endocrinology

      Volume: 14

    • DOI

      10.3389/fendo.2023.1245573

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unmasked insulinoma occasioned by severe hypoglycemic coma immediately postpartum: a case report2023

    • Author(s)
      Matsumoto Kiyoshi、Watanabe Miyu、Takao Ken、Takahashi Hirokazu、Daido Hisashi、Shibata Toshiro、Hirose Tokuyuki、Kato Takehiro、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Murakami Takaaki、Yabe Daisuke
    • Journal Title

      BMC Endocrine Disorders

      Volume: 23 Issue: 1 Pages: 168-168

    • DOI

      10.1186/s12902-023-01415-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noninvasive evaluation of donor and native pancreases following simultaneous pancreas?kidney transplantation using positron emission tomography/computed tomography2023

    • Author(s)
      Murakami Takaaki、Nakamura Toshihiro、Fujimoto Hiroyuki、Fujikura Junji、Shimizu Yoichi、Miyake Kanae K.、Otani Daisuke、Sakaki Kentaro、Kiyobayashi Sakura、Anazawa Takayuki、Nakamoto Yuji、Inagaki Nobuya
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 14 Issue: 10 Pages: 1187-1191

    • DOI

      10.1111/jdi.14045

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noninvasive quantitative evaluation of viable islet grafts using <scp> <sup>111</sup> In </scp> ‐exendin‐4 <scp>SPECT</scp> / <scp>CT</scp>2023

    • Author(s)
      Botagarova Ainur、Murakami Takaaki、Fujimoto Hiroyuki、Fauzi Muhammad、Kiyobayashi Sakura、Otani Daisuke、Fujimoto Nanae、Inagaki Nobuya
    • Journal Title

      The FASEB Journal

      Volume: 37 Issue: 4 Pages: 1-11

    • DOI

      10.1096/fj.202201787rr

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current understanding of imeglimin action on pancreatic β‐cells: Involvement of mitochondria and endoplasmic reticulum homeostasis2022

    • Author(s)
      Fauzi Muhammad、Murakami Takaaki、Yabe Daisuke、Inagaki Nobuya
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 14 Issue: 2 Pages: 186-188

    • DOI

      10.1111/jdi.13951

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preservation effect of imeglimin on pancreatic β-cell mass: Noninvasive evaluation using 111In-exendin-4 SPECT/CT imaging and the perspective of mitochondrial involvements2022

    • Author(s)
      Fauzi Muhammad、Murakami Takaaki、Fujimoto Hiroyuki、Botagarova Ainur、Sakaki Kentaro、Kiyobayashi Sakura、Ogura Masahito、Inagaki Nobuya
    • Journal Title

      Frontiers in Endocrinology

      Volume: 13 Pages: 1-12

    • DOI

      10.3389/fendo.2022.1010825

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2022-04-19   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi