Elucidation of mechanism of transdifferentiation of pancreatic acinar cells into insulin-secreting cells

• Project/Area Number: 18590983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University (2007-2008); Kyoto University (2006)
• Principal Investigator: MINAMI Kohtaro Kobe University, 大学院・医学研究科, 准教授 (80334176)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: エネルギー / 糖代謝異常 / 再生医療 / 膵線房細胞 / インスリン / 膵β細胞 / 糖尿病 / 細胞間接着 / 膵腺房細胞

Research Abstract

インスリンを分泌する細胞を人工的に作製することは糖尿病の根治療法の開発に結びつく可能性があり社会的意義は大きい。研究代表者はすでに、膵臓で最も大量に存在する腺房細胞(消化酵素を産生・分泌する細胞)をインスリン分泌細胞へ変化させることに成功していたが、本研究ではそのメカニズムを解析し、細胞同士の接着が一旦破壊されて再度形成されることが、細胞特性の変化をもたらす原因であることを初めて明らかにした。

Research Products

• [Journal Article] Role of cadherin-mediated cell-cell adhesion in pancreatic exocrine-to-endocrine transdifferentiation. (2008)
  • Author(s): Minami K, Okano H, Okumachi A, and Seino S.
  • Journal Title: J Biol Chem 283 Pages: 13753-13761
  • Peer Reviewed
• [Journal Article] Pancreatic acinar-to-beta cell transdifferentiation in vitro (2008)
  • Author(s): Minami K and Seino S.
  • Journal Title: Front Biosci 13 Pages: 5824-5837
  • Peer Reviewed
• [Journal Article] 膵・細胞の機能、再生と幹/前駆細胞 (2008)
  • Author(s): 南幸太郎、清野進
  • Journal Title: アンチエイジング医学 4 Pages: 790-794
• [Journal Article] 糖尿病治療における再生医学の可能性 (2008)
  • Author(s): 南幸太郎、清野進
  • Journal Title: BioClinica 23 Pages: 366-370
• [Journal Article] 膵臓の再生 (2008)
  • Author(s): 南幸太郎、清野進
  • Journal Title: 日本臨床 66 Pages: 926-931
• [Journal Article] Role of cadherin-mediated cell-cell adhesion in pancreatic exocrine-to-endocrine transdifferentiation. (2008)
  • Author(s): Minami K, et al.
  • Journal Title: Journal of Biological Chemistry 283 Pages: 13753-13761
  • Peer Reviewed
• [Journal Article] Pancreatic acinar-to-beta cell transdifferentiation in vitro. (2008)
  • Author(s): Minami K, Seino S
  • Journal Title: Frontiers in Bioscience 13 Pages: 5824-5837
  • Peer Reviewed
• [Journal Article] 膵臓の再生 (2008)
  • Author(s): 南幸太郎, 清野進
  • Journal Title: 日本臨床 66 Pages: 926-931
• [Journal Article] 糖尿病治療における再生医学の可能性 (2008)
  • Author(s): 南幸太郎, 消野進
  • Journal Title: BioClinica 23 Pages: 366-370
• [Journal Article] 膵β細胞の機能、再生と幹/前駆細胞 (2008)
  • Author(s): 南幸太郎, 清野進
  • Journal Title: アンチエイジング医学 4 Pages: 790-794
• [Journal Article] Induction by NeuroD of the components required for regulated exocytosis. (2007)
  • Author(s): Ishizuka N, Minami K, Okumachi A, Okuno M, and Seino S.
  • Journal Title: Biochem Biophys Res Commun 354 Pages: 271-277
  • Peer Reviewed
• [Journal Article] Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes. (2007)
  • Author(s): Okuno M, Minami K (equal contribution), Okumachi A, Miyawaki K, Toyokuni S, and Seino S.
  • Journal Title: Am J Physiol Endocrinol Metab 292
  • Peer Reviewed
• [Journal Article] インスリン分泌におけるユビキチン-プロテアソーム系の役割 (2007)
  • Author(s): 川口美穂、南幸太郎、清野進
  • Journal Title: 内内分泌・糖尿病科 25 Pages: 250-257
• [Journal Article] 膵腺房細胞からインスリン分泌細胞への分化転換 (2007)
  • Author(s): 南幸太郎、清野進
  • Journal Title: 医学のあゆみ 220 Pages: 1145-1148
• [Journal Article] Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes. (2007)
  • Author(s): Okuno M, Minami K, Okumachi A, Miyawaki K, Toyokuni S, Seino S.
  • Journal Title: American Journal of Physiology-Endocrinology and Metabolism 292(1)
• [Journal Article] Induction by NeuroD of the components required for regulated exocytosis. (2007)
  • Author(s): Ishizuka N, Minami K, Okumachi A, Okuno M, Seino S.
  • Journal Title: Biochemical and Biophysical Research Communications 354(1) Pages: 271-277
• [Journal Article] Spontaneous recovery from hyperglycemia by regeneration of pancreatic ・-cells in Kir6 (2006)
  • Author(s): Oyama K, Minami K, Ishizaki K, Miki T, and Seino S.
  • Journal Title: 2G132S transgenic mice. Diabetes 55 Pages: 1930-1938
  • Peer Reviewed
• [Journal Article] Essential role of ubiquitin-proteasome system in normal regulation of insulin secretion (2006)
  • Author(s): Kawaguchi M, Minami K (equal contribution), Nagashima K, and Seino S.
  • Journal Title: J Biol Chem 281 Pages: 13015-13020
  • Peer Reviewed
• [Journal Article] 膵腺房細胞の分化転換によるインスリン分泌細胞の誘導 (2006)
  • Author(s): 南幸太郎、清野進
  • Journal Title: 最新医学 61 Pages: 1496-1501
• [Journal Article] 膵幹細胞からの再生 (2006)
  • Author(s): 南幸太郎、清野進
  • Journal Title: Diabetes Frontier 17 Pages: 314-318
• [Journal Article] Essential role of ubiquitin-proteasome system in normal regulation of insulin secretion. (2006)
  • Author(s): Kawaguchi M, Minami K, Nagashima K, Seino S.
  • Journal Title: Journal of Biological Chemistry 281(19) Pages: 10315-13020
• [Journal Article] Spontaneous recovery from hyperglycemia by regeneration of pancreatic β-cells in Kir6.2G132S transgenic mice. (2006)
  • Author(s): Oyama K, Minami K, Ishizaki K, Miki T, Seino S.
  • Journal Title: Diabetes 55(7) Pages: 1930-1938
• [Journal Article] 膵腺房細胞の分化転換によるインスリン分泌細胞の誘導 (2006)
  • Author(s): 南幸太郎, 清野進
  • Journal Title: 最新医学 61(7) Pages: 1496-1501
• [Journal Article] 膵幹細胞からの再生 (2006)
  • Author(s): 南幸太郎, 清野進
  • Journal Title: Diabetes Frontier 17(3) Pages: 314-318
• [Journal Article] Role of cadherin-mediated cell-cell adhesion in pancreatic acinar-to-endocrine transdifferentiation.
  • Author(s): Minami K, et. al.
  • Journal Title: Journal of Biological Chemistry (印刷中)
  • Peer Reviewed
• [Journal Article] Pancreatic acinar-to-beta cell transdifferentiation in vitro.
  • Author(s): Minami K and Seino S
  • Journal Title: Frontiers in Bioscience (印刷中)
  • Peer Reviewed
• [Presentation] A novel strategy for in vitro cell tracing reveals phenotypic reversibility of mouse pancreatic beta-cells (2009)
  • Author(s): Minami K, Miyawaki K, Seino S.
  • Organizer: EMBO Workshop : Beta cell differentiation and regeneration
  • Place of Presentation: Peebles, UK
  • Year and Date: 2009-02-28
• [Presentation] Induction of insulin-secreting cells from pancreatic acinar cells in vitro and its mechanism (2009)
  • Author(s): Seino S, Hagiwara Y, Minami K.
  • Organizer: EMBO Workshop : Beta cell differentiation and regeneration
  • Place of Presentation: Peebles, UK
  • Year and Date: 2009-02-28
• [Presentation] A novel strategy for in vitro cell tracing reveals phenotypic reversibility of mouse pancreatic beta-cells (2009)
  • Author(s): Minami K, et al.
  • Organizer: EMBO Workshop, Beta Cell Differentiation and Regeneration
  • Place of Presentation: イギリス・Peebles
  • Year and Date: 2009-02-28
• [Presentation] Mechanism of pancreatic exocrine-to-endocrine transdifferentiation (2008)
  • Author(s): Minami K.
  • Organizer: Asia Islet Biology & Incretin Symposium
  • Place of Presentation: Incheon
  • Year and Date: 2008-10-19
• [Presentation] Mechanism of pancreatic exocrine-to-endocrine transdifferentiation. (2008)
  • Author(s): Minami K.
  • Organizer: Asia Islet Biology & Incretin Symposium
  • Place of Presentation: 韓国・インチョン
  • Year and Date: 2008-10-19
• [Presentation] Role of cadherin-mediated cell-cell adhesion in transdifferentiation of pancreatic acinar cells (2008)
  • Author(s): Minami K, Okano H, and Seino S.
  • Organizer: 44th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Rome
  • Year and Date: 2008-09-08
• [Presentation] Role of cadherin-mediated cell-cell adhesion in transdifferentiation of pancreatic acinar cells. (2008)
  • Author(s): Minami K, Okano H, Scino S
  • Organizer: 44th Annual Meeting of the European Association for theStudy of Diabetes
  • Place of Presentation: イタリア・ローマ
  • Year and Date: 2008-09-08
• [Presentation] and Seino S. Signaling mechanism of in vitro transdifferentiation of pancreatic acinar cells. (2008)
  • Author(s): Minami K.
  • Organizer: 6th Catholic International Stem Cell Symposium
  • Place of Presentation: Seoul
  • Year and Date: 2008-06-20
• [Presentation] Signaling mechanism of in vitro transdifferenliation of pancreatic acinar cells. (2008)
  • Author(s): Minami K, Seino S
  • Organizer: 6th Catholic International Stem Cell Symposium
  • Place of Presentation: 韓国・ソウル
  • Year and Date: 2008-06-20
• [Presentation] カドヘリン依存性細胞接着による膵細胞分化転換制御 (2008)
  • Author(s): 南幸太郎、岡野宏俊、清野進
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] 血糖値回復に至るための膵β細胞再生機構の解明 (2008)
  • Author(s): 尾山和信、川口美穂、鏑木康志、南幸太郎、三木隆司、清野進、安田和基
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] 膵β細胞再生へのアプローチ (2008)
  • Author(s): 南幸太郎
  • Organizer: 第48回三九会
  • Place of Presentation: 神戸
  • Year and Date: 2008-03-29
• [Presentation] Strategies for regeneration of pancreatic ・-cells (2007)
  • Author(s): 南幸太郎
  • Organizer: 第9回インスリンリサーチフォーラム
  • Place of Presentation: 大阪
  • Year and Date: 2007-11-17
• [Presentation] Phenotypic plasticity of pancreatic cells (2007)
  • Author(s): 南幸太郎、宮脇一真、奥野正顕、清野進
  • Organizer: 第25回内分泌代謝学サマーセミナー
  • Place of Presentation: 淡路
  • Year and Date: 2007-07-17
• [Presentation] 膵腺房細胞における分化の可塑性 (2007)
  • Author(s): 南幸太郎、岡野宏俊、奥町彰礼、石塚伸子、清野進
  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-06-15
• [Presentation] 膵線房細胞における分化の可塑性 (2007)
  • Author(s): 南幸太郎, ら
  • Organizer: 日本内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2007-06-15
• [Presentation] Plasticity of pancreatic cells (2007)
  • Author(s): Minami K. Miyawaki K, Okuno M, and Seino S.
  • Organizer: 19th FAOBMB
  • Place of Presentation: Seoul
  • Year and Date: 2007-05-28
• [Presentation] Plasticity of pancreatic cells. (2007)
  • Author(s): Minami K, et. al.
  • Organizer: Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB)
  • Place of Presentation: 韓国(ソウル)
  • Year and Date: 2007-05-28
• [Presentation] 転写因子NeuroDによる調節性開口放出機能誘導 (2007)
  • Author(s): 石塚伸子、南幸太郎、奥町彰礼、奥野正顕、清野進
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-26
• [Presentation] シンポジウム「膵島移植と再生」 : 膵細胞の可塑性 (2007)
  • Author(s): 南幸太郎、宮脇一真、奥野正顕、清野進
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Presentation] 膵細胞の可塑性 (2007)
  • Author(s): 南幸太郎, ら
  • Organizer: 日本糖尿病学会(シンポジウム)
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Presentation] Kir6. 2G132Sトランスジェニックマウスにおける膵β細胞再生機構 (2006)
  • Author(s): 尾山和信、南幸太郎、石崎勝彦、布施雅規、三木隆司、清野進
  • Organizer: 日本分子生物学会2006フォーラム
  • Place of Presentation: 名古屋
  • Year and Date: 2006-12-07
• [Book] Kir6.2G132S TGマウス : in vivoにおける膵・細胞再生のモデル (2008)
  • Author(s): 尾山和信、南幸太郎、三木隆司、清野進
  • Publisher: 分子糖尿病学の進歩基礎から臨床まで-2008金原出版
• [Book] 膵腺房細胞の分化転換によるインスリン分泌細胞の作出 (2007)
  • Author(s): 南幸太郎、奥野正顕、宮脇一真、清野進
  • Publisher: 糖尿病学2007診断と治療社
• [Book] 膵腺房細胞の分化転換による・細胞再生の可能性 (2007)
  • Author(s): 南幸太郎、清野進
  • Publisher: 分子糖尿病学の進歩基礎から臨床まで-2008金原出版
• [Book] 糖尿病学2007 (2007)
  • Author(s): 南幸太郎, ら
  • Publisher: 膵腺房細胞の分化転換によるインスリン分泌細胞の作出
• [Book] 分子糖尿病学の進歩 (2007)
  • Author(s): 南幸太郎、清野進
  • Publisher: 膵腺房細胞の分化転換によるβ細胞再生の可能性