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2022 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number 21K19504
Research InstitutionGifu University

Principal Investigator

矢部 大介  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
Keywords膵β細胞量 / βFucciマウス / 低分子化合物 / スクリーニング
Outline of Annual Research Achievements

膵ベータ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。特に日本人を含む東アジア人は、他民族と比してインスリン分泌量が低いためインスリン分泌障害の問題はなお深刻である。本研究では、膵β増殖をリアルタイムに観察可能なベータFucciマウス(Diabetes. 2020 Nov;69(11):2340-2351)を樹立し、その単離膵島細胞を3次元培養もしくは2次元で最長1週間の間、ex vivoで培養することに成功した。特に2次元培養においては、種々のプレートを検討するなかで、日本ジェネティクス社製マイクロSlide I Luerを用いることで安定して培養が可能かつ、11.1 mMグルコースを含むRPMIに膵ベータ細胞増殖作用が知られるDYRK阻害薬のひとつHarmineを添加することで、ex vivoにおいてもベータFucciマウス由来膵ベータ細胞が増殖することを確認しえた。一方、膵ベータ細胞増殖を誘導する目的でグルコース濃度を20.0 mMまで上昇させるもしくは、GKA活性薬を添加した場合にはベータFucciマウス由来膵ベータ細胞の増殖は認めなかった。現在、樹立したアッセイ系を用いて低分子化合物(低分子化合物ライブラリー(Sigma-aldrich社既知の阻害剤1,200化合物、GPCRをターゲットにした指向性ライブラリー 2,000化合物、ChemDiv社drug-like構造多様性ライブラリー約10,000化合物を含む)をスクリーニングしている。

  • Research Products

    (38 results)

All 2023 2022

All Journal Article (26 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 26 results,  Open Access: 23 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 10 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Increased expression of glucagon-like peptide-1 and cystic fibrosis transmembrane conductance regulator in the ileum and colon in mouse treated with metformin2023

    • Author(s)
      Mizoguchi Momoka、Takemori Hiroshi、Furukawa Saho、Ito Masafumi、Asai Mutsumi、Morino Hirofumi、Miura Takanori、Yabe Daisuke、Shibata Takashi
    • Journal Title

      Endocrine Journal

      Volume: 70 Pages: 149~159

    • DOI

      10.1507/endocrj.EJ22-0260

    • Peer Reviewed / Open Access
  • [Journal Article] Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study2023

    • Author(s)
      Karasik Avraham、Lanzinger Stefanie、Chia-Hui Tan Elise、Yabe Daisuke、et al.
    • Journal Title

      Diabetes & Metabolism

      Volume: 49 Pages: 101418~101418

    • DOI

      10.1016/j.diabet.2022.101418

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Makoto、Ohno Yuko、Ikeda Asuka、Godai Kayo、Li Yaya、Nakamura Yuko、Yabe Daisuke、Tsushita Kazuyo、Kashihara Naoki、Kamide Kei、Kabayama Mai
    • Journal Title

      Hypertension Research

      Volume: 46 Pages: 1075~1089

    • DOI

      10.1038/s41440-023-01185-2

    • Peer Reviewed / Open Access
  • [Journal Article] Empagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in routine care in East Asia: Results from the <scp>EMPRISE</scp> study2023

    • Author(s)
      Kim Dae Jung、Sheu Wayne H‐H、Chung Wook‐Jin、Yabe Daisuke、Ha Kyoung Hwa、Nangaku Masaomi、Tan Elise Chia‐Hui、Node Koichi、Yasui Atsutaka、Lei Weiyu、Lee Sunwoo、Saarelainen Laura、Deruaz‐Luyet Anouk、Kyaw Moe H、Seino Yutaka、EMPRISE East Asia Study Group
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 14 Pages: 417~428

    • DOI

      10.1111/jdi.13959

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two cases of systemic lupus erythematosus after administration of severe acute respiratory syndrome coronavirus 2 vaccine2023

    • Author(s)
      Sakai Mayu、Takao Ken、Mizuno Masami、Ando Hironori、Kawashima Yui、Kato Takehiro、Kubota Saki、Hirose Tokuyuki、Hirota Takuo、Horikawa Yukio、Yabe Daisuke
    • Journal Title

      Modern Rheumatology Case Reports

      Volume: In press Pages: -

    • DOI

      10.1093/mrcr/rxad008

    • Peer Reviewed / Open Access
  • [Journal Article] Erdheim-Chester Disease With BRAF V600E Mutation and Central Diabetes Insipidus Successfully Treated With Glucocorticoid2023

    • Author(s)
      Imaizumi Toshinori、Daido Hisashi、Kato Takehiro、Yabe Daisuke
    • Journal Title

      JCEM Case Reports

      Volume: 1 Pages: luad014

    • DOI

      10.1210/jcemcr/luad014

    • Peer Reviewed / Open Access
  • [Journal Article] Glucose‐dependent insulinotropic polypeptide counteracts diet‐induced obesity along with reduced feeding, elevated plasma leptin and activation of leptin‐responsive and proopiomelanocortin neurons in the arcuate nucleus2023

    • Author(s)
      Han Wanxin、Wang Lei、Ohbayashi Kento、Takeuchi Masakazu、O'Farrell Libbey、Coskun Tamer、Rakhat Yermek、Yabe Daisuke、Iwasaki Yusaku、Seino Yutaka、Yada Toshihiko
    • Journal Title

      Diabetes, Obesity and Metabolism

      Volume: 25 Pages: 1534~1546

    • DOI

      10.1111/dom.15001

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Pages: -

    • Peer Reviewed / Open Access
  • [Journal Article] Device-supported automated basal insulin titration in adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials2023

    • Author(s)
      Luo Yingying、Chang Yaping、Zhao Zhan、Xia Jun、Xu Chenchen、Bee Yong Mong、Li Xiaoying、Sheu Wayne H.-H.、McGill Margaret、Chan Siew Pheng、Deodat Marisa、Suastika Ketut、Thy Khue Nguyen、Chen Liming、Shan Kong Alice Pik、Chen Wei、Deerochanawong Chaicharn、Yabe Daisuke、Zhao Weigang、Lim Soo、Yao Xiaomei、Ji Linong
    • Journal Title

      The Lancet Regional Health - Western Pacific

      Volume: In press Pages: -

    • DOI

      10.1016/j.lanwpc.2023.100746

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glucokinase-maturity onset diabetes mellitus in the young suggested by factory-calibrated glucose monitoring data: a case report2022

    • Author(s)
      Nomura Nao、Iizuka Katsumi、Goshima Eiichi、Hosomichi Kazuyoshi、Tajima Atsushi、Kubota Sodai、Liu Yanyan、Takao Ken、Kato Takehiro、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Yabe Daisuke
    • Journal Title

      Endocrine Journal

      Volume: 69 Pages: 473~477

    • DOI

      10.1507/endocrj.EJ21-0526

    • Peer Reviewed
  • [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 Pages: 810~821

    • DOI

      10.1111/jdi.13728

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Graves' Disease with Thymic Hyperplasia: The Response of the Thyroid Function, Thyrotropin Receptor Autoantibody, and Thymic Size to Thiamazole Treatment2022

    • Author(s)
      Tsukada Daichi、Iizuka Katsumi、Takao Ken、Liu Yanyan、Kubota Sodai、Okamoto-Kubota Saki、Sakurai Teruaki、Imaizumi Toshinori、Sakai Mayu、Kato Takehiro、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Yamamoto Mayumi、Kubota Sumihisa、Yabe Daisuke
    • Journal Title

      Internal Medicine

      Volume: 61 Pages: 2753~2757

    • DOI

      10.2169/internalmedicine.8710-21

    • Peer Reviewed / Open Access
  • [Journal Article] Graves' Disease after Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine in a Type 1 Diabetes Patient2022

    • Author(s)
      Sakai Mayu、Takao Ken、Kato Takehiro、Ito Kodai、Kubota Sodai、Hirose Tokuyuki、Liu Yanyan、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Yabe Daisuke
    • Journal Title

      Internal Medicine

      Volume: 61 Pages: 1561~1565

    • DOI

      10.2169/internalmedicine.9231-21

    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and safety of oral semaglutide in Japanese patients with type?2 diabetes: A subgroup analysis by baseline variables in the PIONEER?9 and PIONEER?10 trials2022

    • Author(s)
      Yabe Daisuke、Deenadayalan Srikanth、Horio Hiroshi、Kaneto Hideaki、Jensen Thomas Bo、Terauchi Yasuo、Yamada Yuichiro、Inagaki Nobuya
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 13 Pages: 975~985

    • DOI

      10.1111/jdi.13764

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type?2 diabetes by baseline age and body mass index2022

    • Author(s)
      Yabe Daisuke、Yamada Yuichiro、Kaku Kohei、Nishida Tomoyuki、Sato Toshihiro、Seino Yutaka
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 13 Pages: 1161~1174

    • DOI

      10.1111/jdi.13773

    • Peer Reviewed / Open Access
  • [Journal Article] High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides2022

    • Author(s)
      Ueno Shinji、Seino Yusuke、Hidaka Shihomi、Maekawa Ryuya、Takano Yuko、Yamamoto Michiyo、Hori Mika、Yokota Kana、Masuda Atsushi、Himeno Tatsuhito、Tsunekawa Shin、Kamiya Hideki、Nakamura Jiro、Kuwata Hitoshi、Fujisawa Haruki、Shibata Megumi、Takayanagi Takeshi、Sugimura Yoshihisa、Yabe Daisuke、et al.
    • Journal Title

      Nutrients

      Volume: 14 Pages: 975~975

    • DOI

      10.3390/nu14050975

    • Peer Reviewed / Open Access
  • [Journal Article] Long-term safety and effectiveness of linagliptin by baseline body mass index in Japanese patients with type 2 diabetes: a 3-year post-marketing surveillance study2022

    • Author(s)
      Yabe Daisuke、Yamamoto Fumiko、Lund S?ren S.、Okamura Tomoo、Kadowaki Takashi
    • Journal Title

      Expert Opinion on Drug Safety

      Volume: 21 Pages: 1303~1313

    • DOI

      10.1080/14740338.2022.2057948

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] D-Allulose cooperates with glucagon-like peptide-1 and activates proopiomelanocortin neurons in the arcuate nucleus and central injection inhibits feeding in mice2022

    • Author(s)
      Yermek Rakhat、Wang Lei、Kaneko Kentaro、Han Wanxin、Seino Yutaka、Yabe Daisuke、Yada Toshihiko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 613 Pages: 159~165

    • DOI

      10.1016/j.bbrc.2022.04.027

    • Peer Reviewed
  • [Journal Article] Semaglutide is effective in type 2 diabetes and obesity with schizophrenia2022

    • Author(s)
      Noda Kaoru、Kato Takehiro、Nomura Nao、Sakai Mayu、Kubota Sodai、Hirose Tokuyuki、Liu Yanyan、Takahashi Yoshihiro、Takao Ken、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Yabe Daisuke
    • Journal Title

      Diabetology International

      Volume: 13 Pages: 693~697

    • DOI

      10.1007/s13340-022-00590-1

    • Peer Reviewed
  • [Journal Article] A case of familial hypocalciuric hypercalcemia type 1 due to CASR p.Pro55Leu mutation2022

    • Author(s)
      Sumida Akira、Iizuka Katsumi、Kato Takehiro、Liu Yanyan、Kubota Sodai、Kubota-Okamoto Saki、Sakurai Teruaki、Imaizumi Toshinori、Takahashi Yoshihiro、Mizuno Masami、Takao Ken、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Yamamoto Mayumi、Seino Yusuke、Suzuki Atsushi、Yabe Daisuke
    • Journal Title

      BMC Endocrine Disorders

      Volume: 22 Pages: 164

    • DOI

      10.1186/s12902-022-01077-5

    • Peer Reviewed / Open Access
  • [Journal Article] Association of cardiovascular disease risk and changes in renin levels by mineralocorticoid receptor antagonists in patients with primary aldosteronism2022

    • Author(s)
      Nomura Motoko、Kurihara Isao、Itoh Hiroshi、Ichijo Takamasa、Katabami Takuyuki、Tsuiki Mika、Wada Norio、Yoneda Takashi、Sone Masakatsu、Oki Kenji、Yamada Tetsuya、Kobayashi Hiroki、Tamura Kouichi、Ogawa Yoshihiro、Inagaki Nobuya、Yamamoto Koichi、Otsuki Michio、Yabe Daisuke、et al.
    • Journal Title

      Hypertension Research

      Volume: 45 Pages: 1476~1485

    • DOI

      10.1038/s41440-022-00960-x

    • Peer Reviewed / Open Access
  • [Journal Article] d-Allulose Inhibits Ghrelin-Responsive, Glucose-Sensitive and Neuropeptide Y Neurons in the Arcuate Nucleus and Central Injection Suppresses Appetite-Associated Food Intake in Mice2022

    • Author(s)
      Rakhat Yermek、Kaneko Kentaro、Wang Lei、Han Wanxin、Seino Yutaka、Yabe Daisuke、Yada Toshihiko
    • Journal Title

      Nutrients

      Volume: 14 Pages: 3117~3117

    • DOI

      10.3390/nu14153117

    • Peer Reviewed / Open Access
  • [Journal Article] Association of dipeptidyl peptidase‐4 inhibitor use and risk of pancreatic cancer in individuals with diabetes in Japan2022

    • Author(s)
      Kubota Sodai、Haraguchi Takuya、Kuwata Hitoshi、Seino Yusuke、Murotani Kenta、Tajima Takumi、Terashima Gen、Kaneko Makiko、Takahashi Yoshihiro、Takao Ken、Kato Takehiro、Shide Kenichiro、Imai Saeko、Suzuki Atsushi、Terauchi Yasuo、Yamada Yuichiro、Seino Yutaka、Yabe Daisuke
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 14 Pages: 67~74

    • DOI

      10.1111/jdi.13921

    • Peer Reviewed / Open Access
  • [Journal Article] Change in pharmacodynamic variables following once‐weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes ( <scp>SURPASS</scp> J‐mono substudy)2022

    • Author(s)
      Yabe Daisuke、Kawamori Dan、Seino Yusuke、Oura Tomonori、Takeuchi Masakazu
    • Journal Title

      Diabetes, Obesity and Metabolism

      Volume: 25 Pages: 398~406

    • DOI

      10.1111/dom.14882

    • 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 Tomonobu、Harada Norio、Tokumoto Shinsuke、Yamane Shunsuke、Ikeguchi-Ogura Eri、Kato Tomoko、Yasuda Takuma、Tatsuoka Hisato、Shimazu-Kuwahara Satoko、Yabe Daisuke、Hayashi Yoshitaka、Inagaki Nobuya
    • Journal Title

      Scientific Reports

      Volume: 12 Pages: 17530

    • DOI

      10.1038/s41598-022-22511-7

    • Peer Reviewed / Open Access
  • [Journal Article] Use of iGlarLixi for Management of Type 2 Diabetes in Japanese Clinical Practice: SPARTA Japan, a Retrospective Observational Study2022

    • Author(s)
      Matsuhisa Munehide、Miyoshi Hideaki、Yabe Daisuke、Takahashi Yoko、Morimoto Yukiko、Terauchi Yasuo
    • Journal Title

      Diabetes Therapy

      Volume: 14 Pages: 219~236

    • DOI

      10.1007/s13300-022-01333-w

    • Peer Reviewed / Open Access
  • [Presentation] DPP-4阻害薬-エビデンスを整理して 日本人での使い方を考える2023

    • Author(s)
      矢部大介、窪田創大、加藤丈博
    • Organizer
      第56回糖尿病学の進歩
    • Invited
  • [Presentation] 超高齢社会における糖尿病食事療法2022

    • Author(s)
      矢部大介
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Invited
  • [Presentation] 高齢者の糖尿病性腎症重症化予防2022

    • Author(s)
      矢部大介
    • Organizer
      第64回日本老年医学会学術集会
    • Invited
  • [Presentation] 肥満2型糖尿病の新しい薬物治療薬-GLP-1受容体作動薬と関連薬剤-2022

    • Author(s)
      矢部大介
    • Organizer
      第22回日本抗加齢医学会総会
    • Invited
  • [Presentation] 新規糖尿病注射治療薬のポテンシャル~糖尿病専門医の立場から~2022

    • Author(s)
      矢部大介
    • Organizer
      第67回日本透析医学会学術集会・総会
    • Invited
  • [Presentation] SGLT2 inhibitor luseogliflozin in the management of type 2 diabetes in Asia2022

    • Author(s)
      Daisuke Yabe
    • Organizer
      39th Diabetes Philippines Annual Convention and Scientific Sessions
    • Int'l Joint Research / Invited
  • [Presentation] SGLT2 inhibitor: beyond glucose lowering effect, cardiometabolic renal axis2022

    • Author(s)
      Daisuke Yabe
    • Organizer
      International Congress on Diabetes and Metabolism 2022
    • Int'l Joint Research / Invited
  • [Presentation] 慣習的に摂取する食事内容と2型糖尿病治療薬の効果2022

    • Author(s)
      矢部大介、加藤丈博、水野正巳
    • Organizer
      第44回日本臨床栄養学会総会/第43回日本臨床栄養協議会/第20回大連合大会
    • Invited
  • [Presentation] GLP-1受容体作動薬2022

    • Author(s)
      矢部大介、窪田創大、小出祐也、加藤丈博
    • Organizer
      第28回日本糖尿病眼学会総会/第37回日本糖尿病合併症学会
    • Invited
  • [Presentation] 糖尿病におけるオンライン診療の実際と課題2022

    • Author(s)
      矢部大介
    • Organizer
      第32回臨床内分泌代謝Update
    • Invited
  • [Book] ガイドラインにないリアル糖尿病薬物療法をガイドする2022

    • Author(s)
      坂根直樹
    • Total Pages
      288
    • Publisher
      新興医学出版社
    • ISBN
      9784880029207
  • [Patent(Industrial Property Rights)] GIP受容体拮抗薬を用いたサルコペニア予防/改善薬2022

    • Inventor(s)
      髙橋侑也、藤田浩樹、山田祐一郎、矢部大介、清野祐介
    • Industrial Property Rights Holder
      髙橋侑也、藤田浩樹、山田祐一郎、矢部大介、清野祐介
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      -

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Published: 2023-12-25  

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