Establishment of an experimental system to evaluate pancreatic beta-cell proliferation in vitro that can be utilized to identify anti-diabetes therapeutics targeting pancreatic beta-cell mass
Project/Area Number |
21K19504
|
Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
|
Research Institution | Gifu University |
Principal Investigator |
Yabe Daisuke 岐阜大学, 大学院医学系研究科, 教授 (60378643)
|
Co-Investigator(Kenkyū-buntansha) |
劉 彦言 岐阜大学, 大学院医学系研究科, 研究員 (10845796)
飯塚 勝美 藤田医科大学, 医学部, 教授 (40431712)
|
Project Period (FY) |
2021-07-09 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
Keywords | 膵β細胞量 / 糖尿病 / 低分子化合物 / スクリーニング / βFucciマウス / MIP-Cre; Fucci2aRマウス / インスリン分泌能 |
Outline of Research at the Start |
血糖値を緻密に制御するインスリンをつくる膵β細胞の減少は糖尿病の発症や重症化を阻止するうえで克服すべき重要な課題です。糖尿病患者では、膵β細胞の量が減少することが示されているため、生体内で膵β細胞の量を増やす技術が待ち望まれています。しかし、膵β細胞の量を制御するメカニズムの全容は依然不明であり、膵β細胞量を標的にした糖尿病の予防や治療の方法も一切存在しません。今回、最近開発した膵β細胞増殖をリアルタイムに観察可能なマウスを用いて、膵β細胞増殖を促す低分子化合物スクリーニングを可能にするアッセイ系を樹立し、膵β細胞増殖薬の創薬標的の同定を目指します。
|
Outline of Final Research Achievements |
In this study, we established βFucci mice in which pancreatic β-proliferation can be observed in real time, and successfully cultured the isolated islet cells ex vivo for up to 1 week in 3D or 2D culture. In 2D culture, we examined various types of plates, and found that the Micro Slide I Luer plate manufactured by Nippon Genetics was the most suitable for stable culture, and the plate was able to contain 11.1 mM glucose in RPMI. We have confirmed that the addition of Harmine, a DYRK inhibitor known to proliferate pancreatic beta cells, to RPMI containing 11.1 mM glucose allows stable culture of pancreatic beta cells ex vivo, and have screened low molecular weight compounds using the assay system we established.
|
Academic Significance and Societal Importance of the Research Achievements |
膵β細胞からのインスリン分泌の障害は糖尿病の発症や重症化を阻止するうえで克服すべき重要な課題である。インスリン分泌量は、個々の膵β細胞がインスリンを分泌する能力(膵β細胞機能)と膵β細胞の絶対量(膵β細胞量)の2つの因子により規定され前者に対しては、インクレチン薬やSU薬、グリニド薬が臨床の場で幅広く使用される。一方、後者に対しては、膵β細胞量調節の分子基盤の全容は依然不明であり、膵β細胞量を標的にした糖尿病の予防や治療の方法も一切存在しない。本研究で確立しえたスクリーニング系は、今後、膵β細胞量を標的とした予防や治療に資するシーズ探索に極めて有用なツールといえる。
|
Report
(3 results)
Research Products
(40 results)
-
-
[Journal Article] Association of dipeptidyl peptidase-4 inhibitor use and risk of pancreatic cancer in individuals with diabetes in Japan2023
Author(s)
Sodai Kubota, Takuya Haraguchi Hitoshi Kuwata, Yusuke Seino, Kenta Murotani, Takumi Tajima, Gen Terashima, Makiko Kaneko, Yoshihiro Takahashi, Ken Takao, Takehiro Kato, Kenichiro Shide, Saeko Imai, Atsushi Suzuki, Yasuo Terauchi, Yuichiro Yamada, Yutaka Seino, and Daisuke Yabe
-
Journal Title
Journal of Diabetes Investigation
Volume: 14
Issue: 1
Pages: 67-74
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Current status of the rapid decline in renal function due to diabetes mellitus and its associated factors: analysis using the National Database of Health Checkups in Japan2023
Author(s)
Fujii M, Ohno Y, Ikeda A, Godai K, Li Y, Nakamura Y, Yabe D, Tsushita K, Kashihara N, Kamide K, Kabayama M
-
Journal Title
Hypertension Research
Volume: in press
Issue: 5
Pages: 1075-1089
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Effect of the Diabetic Nephropathy Aggravation Prevention Program on medical visit behavior in individuals using national health insurance in Japan.2023
Author(s)
Ikeda A, Fujii M, Ohno Y, Godai K, Li Y, Nakamura Y, Yabe D, Tsushita K, Kashihara N, Kamide, K, Kabayama M.
-
Journal Title
Journal of Diabetes Investigation
Volume: In press
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Glucokinase-maturity onset diabetes mellitus in the young suggested by factory-calibrated glucose monitoring data: a case report2022
Author(s)
Nao Nomura, Katsumi Iizuka, Eiichi Goshima, Kazuyoshi Hosomichi, Atsushi Tajima, Sodai Kubota, Yanyan Liu, Ken Takao, Takehiro Kato, Masami Mizuno, Takuo Hirota, Tetsuya Suwa, Yukio Horikawa, Daisuke Yabe
-
Journal Title
Endocrine Journal
Volume: 69
Issue: 4
Pages: 473-477
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Healthcare resource utilization in patients treated with empagliflozin in East Asia2022
Author(s)
Sheu Wayne H‐H、Seino Yutaka、Tan Elise Chia‐Hui、Yabe Daisuke、Ha Kyoung Hwa、Nangaku Masaomi、Chung Wook‐Jin、Node Koichi、Yasui Atsutaka、Lei Wei‐Yu、Lee Sunwoo、Ustyugova Anastasia、Klement Riho、Deruaz‐Luyet Anouk、Kyaw Moe H、Kim Dae Jung、the EMPRISE East Asia study group
-
Journal Title
Journal of Diabetes Investigation
Volume: 13
Issue: 5
Pages: 810-821
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
[Journal Article] Association of cardiovascular disease risk and changes in renin levels by mineralocorticoid receptor antagonists in patients with primary aldosteronism2022
Author(s)
Nomura M, Kurihara I, Itoh H, Ichijo T, Katabami T, Tsuiki M, Wada N, Yoneda T, Sone M, Oki K, Yamada T, Kobayashi H, Tamura K, Ogawa Y, Inagaki N, Yamamoto K, Otsuki M, Yabe D, Izawa S, Takahashi Y, Suzuki T, Yasoda A, Tanabe A, Naruse M
-
Journal Title
Hypertension Research
Volume: 45
Issue: 9
Pages: 1476-1485
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] An analysis of intestinal morphology and incretin-producing cells using tissue optical clearing and 3-D imaging2022
Author(s)
Hatoko T, Harada N, Tokumoto S, Yamane S, Ikeguchi-Ogura E, Kato T, Yasuda T, Tatsuoka H, Shimazu-Kuwahara S, Yabe D, Hayashi Y, Inagaki N.
-
Journal Title
Sci Rep.
Volume: 12
Issue: 1
Pages: 17530-17530
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-