Elucidation of the mechanism of pancreatic beta-cell differentiation and regeneration using inducible cell labeling system

• Project/Area Number: 24591330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University
• Principal Investigator: MIANMI KOHTARO 神戸大学, 医学(系)研究科(研究院), 准教授 (80334176)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 糖尿病 / 糖代謝異常 / 膵β細胞 / 再生医療

Outline of Final Research Achievements

In the present study, we chased the fate of pancreatic beta cells by utilizing inducible cell labeling system. In alloxan-induced diabetic mice, the human GLP-1 receptor agonist liraglutide restored function and mass of beta cells. Liraglutide increased beta cell proliferation and decreased beta cell death, but did not induce neogenesis of beta cells.

Research Products

• [Journal Article] Preferential gene expression and epigenetic memory of induced pluripotent stem cells derived from mouse pancreas (2015)
  • Author(s): Nukaya, D., Minami, K., Hoshikawa, R., Yokoi, N., Seino, S.
  • Journal Title: Genes Cells Volume: 印刷中 Issue: 5 Pages: 367-381
  • DOI: 10.1111/gtc.12227
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Liraglutide improves pancreatic beta cell mass and function in alloxan-induced diabetic mice. (2015)
  • Author(s): Tamura K, Minami K, Kudo M, Iemoto K, Takahashi H, Seino S
  • Journal Title: Plos One Volume: 10
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 膵再生 (2015)
  • Author(s): 南幸太郎
  • Journal Title: 肝胆膵 Volume: 70 Pages: 441-446
• [Journal Article] Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action to amplify insulin secretion (2014)
  • Author(s): Gheni G, Ogura M, Iwasaki M, Yokoi N, Minami K, Nakayama Y, Harada K, Hastoy B, Wu X, Takahashi H, Kimura K, Matsubara T, Hoshikawa R, Hatano N, Sugawara K, Shibasaki T, Inagaki N, Bamba T, Mizoguchi A, Fukusaki E, Rorsman P, Seino S
  • Journal Title: Cell Rep Volume: 9 Issue: 2 Pages: 661-673
  • DOI: 10.1016/j.celrep.2014.09.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 膵腺房細胞から膵β細胞への分化転換 (2014)
  • Author(s): 南幸太郎
  • Journal Title: 胆と膵 Volume: 35 Pages: 333-338
• [Journal Article] 膵臓の分化・再生研究の最前線 (2014)
  • Author(s): 南幸太郎
  • Journal Title: 日本消化器学会誌 Volume: 111 Pages: 1543-1549
  • NAID: 130004678076
• [Journal Article] Searching for stem cells in the adult pancreas: A futile effort? (2013)
  • Author(s): Minami K
  • Journal Title: Journal of Diabetes Investigation Volume: 4 Issue: 4 Pages: 331-333
  • DOI: 10.1111/jdi.12061
  • Peer Reviewed
• [Journal Article] GATA transcription factors: new key regulators in pancreas organogenesis. (2013)
  • Author(s): Minami K
  • Journal Title: Journal of Diabetes Investigation Volume: 4 Issue: 5 Pages: 426-427
  • DOI: 10.1111/jdi.12089
  • Peer Reviewed
• [Journal Article] Conditional hypovascularization and hypoxia in islets does not overtly influence adult beta cell mass and function. (2013)
  • Author(s): D’Hoker J, De Leu N, Heremans Y, Baeyens L, Minami K, Ying C, Lavens A, Chintinne M, Stange G, Magenheim J, Swisa A, Martens G, Pipeleers D, van de Casteele M, Seino S, Keshet E, Dor Y, Himberg H
  • Journal Title: Diabetes Volume: 62 Issue: 12 Pages: 4165-4173
  • DOI: 10.2337/db12-1827
  • Peer Reviewed
• [Journal Article] 膵β細胞の機能分化と再生誘導 (2013)
  • Author(s): 南 幸太郎
  • Journal Title: 腎と透析 Volume: 75 Pages: 263-267
• [Journal Article] Current status of regeneration of pancreatic -cells. (2013)
  • Author(s): Minami K, Seino S
  • Journal Title: Journal of Diabetes Investigation Volume: 4 Issue: 2 Pages: 131-141
  • DOI: 10.1111/jdi.12062
  • Peer Reviewed
• [Journal Article] 膵β細胞におけるインスリン分泌制御メカニズム (2012)
  • Author(s): 南幸太郎、清野進
  • Journal Title: 最新臨床糖尿病学（上）―糖尿病学の最新動向－ Volume: NA Pages: 95-98
• [Presentation] アロキサン糖尿病マウスにおけるリラグルチドの膵β細胞に対する効果 (2015)
  • Author(s): 田村香楠子、南幸太郎、高橋晴美 工藤麻耶、北野谷寿人、清野 進
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-22
• [Presentation] マウス膵外分泌細胞からのiPS細胞の樹立と特性解析 (2015)
  • Author(s): 南幸太郎、糠谷大樹、前田治代、星川律子、横井伯英、清野進
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-22
• [Presentation] Preferential expression of liver specific genes and epigenetic memory of induced pluripotent stem cells derived from mouse exocrine pancreas. (2014)
  • Author(s): Minami K, Nukaya D, Hoshikawa R, Yokoi N, Seino S
  • Organizer: 10th IDF-WPR Congress 2014/6th AASD Scientific Meeting
  • Place of Presentation: Suntec, Singapore
  • Year and Date: 2014-11-21
• [Presentation] 膵β細胞の3次元化によるインクレチン/cAMP応答性の誘導 (2014)
  • Author(s): 柴崎忠雄、吾甫尓江艾尼、マヒラアシム、岩崎真宏、星川律子、横井伯英、南幸太郎、清野進
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-16
• [Presentation] Effect of liraglutide on beta-cell mass and function in alloxan diabetic mice. (2014)
  • Author(s): Tamura K, Minami K, Takahashi H, Kudo M, Seino S
  • Organizer: 50th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2014-09-18
• [Presentation] 膵細胞の可塑性と再生医療への応用可能性 (2014)
  • Author(s): 南幸太郎
  • Organizer: 第4回細胞再生医療研究会
  • Place of Presentation: 神戸
  • Year and Date: 2014-07-27
• [Presentation] 膵β細胞におけるグルタミン酸動態の代謝フラックス解析 (2014)
  • Author(s): 吾甫尓江艾尼、横井伯英、星川律子、山口拓郎、岩崎真宏、小倉雅仁、南幸太郎、柴崎忠雄、清野進
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-24
• [Presentation] Evaluation of the effect of liraglutide on beta cell fate in alloxan diabetic mice by tamoxifen-inducible Cre/loxP system.
  • Author(s): Tamura K, Minami K, Takahashi H, Kudo M, Kitanoya H, Seino S
  • Organizer: 49th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Barcelona, Spain
• [Presentation] The role of malate-aspartate shuttle-derived glutamate in incretin-potentiated insulin secretion.
  • Author(s): Ogura M, Iwasaki M, Gheni G, Minami K, Yokoi N, Shibasaki T, Seino S
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Ins2-CreER/R26R-YFPダブルノックインマウスを用いた出生後における新生膵β細胞の運命追跡
  • Author(s): 田村香楠子、南幸太郎、工藤麻耶、北野谷寿人、中村維文、家本啓佑、清野進
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] アロキサン誘導糖尿病マウスの膵細胞に対するリラグルチドの効果
  • Author(s): 工藤麻耶、南幸太郎、田村香楠子、北野谷寿人、家本啓佑、高橋晴美、清野進
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Induction of cAMP responsiveness by formation of pseudoislets.
  • Author(s): Gheni G, Iwasaki M, Ogura M, Yokoi N, Shibasaki T, Minami K, and Seino S
  • Organizer: Beta Cell Workshop 2013 Kyoto
  • Place of Presentation: 京都
• [Presentation] Effect of liraglutide on pancreatic beta-cell mass in alloxan induced diabetic mice.
  • Author(s): Kudo M, Minami K, Tamura K, Kitanoya H, Iemoto K, Takahashi H, and Seino S
  • Organizer: Beta Cell Workshop 2013 Kyoto
  • Place of Presentation: 京都
• [Presentation] Elucidation of postnatal pancreatic beta-cell fate using Ins2-CreER/R26R-YFP double knock-in mice.
  • Author(s): Tamura K, Minami K, Kudo M, Kitanoya H, Nakamura K, and Seino S
  • Organizer: Beta Cell Workshop 2013 Kyoto
  • Place of Presentation: 京都
• [Presentation] タモキシフェン誘導性細胞標識システムを用いた膵β細胞の運命追跡
  • Author(s): 南幸太郎、清野進
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Progranulin (PGRN)：インスリン抵抗性を惹起する新規アディポカイン
  • Author(s): 松原稔哉、三田綾子、南幸太郎、細岡哲也、北澤荘平、高橋健一、田守義和、横井伯英、西村紀、清野進
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] Ins2-CreER/R26R-YFPダブルノックインマウスを用いた出生後における膵β細胞の特性分析
  • Author(s): 田村香楠子、南幸太郎、中村維文、家本啓佑、清野進
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 膵β細胞におけるインクレチン/cAMPシグナルとグルコース代謝の相互作用
  • Author(s): 小倉雅仁、 岩崎真宏、吾甫尔江 艾尼、南幸太郎、柴崎忠雄、中山泰宗、原田和生、馬場健史、三木隆司、宮崎純一、福崎英一郎、清野進
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 膵細胞間相互作用によるインクレチン/cAMPシグナル応答性の誘導
  • Author(s): 吾甫尓江艾尼、岩崎真宏、小倉雅仁、柴崎忠雄、南幸太郎、清野進
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Book] 膵島の再生医療 (2015)
  • Author(s): 南幸太郎
  • Total Pages: 200
  • Publisher: 診断と治療社
• [Book] International Textbook of Diabetes Mellitus (ITDM), 4th edition (2015)
  • Author(s): Seino S, Shibasaki T, Minami K
  • Total Pages: 1240
  • Publisher: Wiley-Blackwell
• [Remarks] 神戸大学細胞分子医学分野
  • URL: http://www.med.kobe-u.ac.jp/phys1/