Elucidation of molecular basis of pancreatic beta-cell regeneration from pancreatic acinar cells

• Project/Area Number: 21591137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University
• Principal Investigator: MINAMI Kohtaro 神戸大学, 大学院・医学研究科, 准教授 (80334176)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: エネルギー / 糖代謝異常 / 再生医療 / 膵腺房細胞 / インスリン / 膵β細胞 / 糖尿病 / 細胞内シグナル

Research Abstract

Generation of surrogate beta-cells(insulin-secreting cells) is a promising approach toward development of regenerative medicine in diabetes mellitus. In this study, it has been shown that insulin-secreting cells can be generated from human pancreatic exocrine cells. It also has been found that pancreatic beta-cells change their phenotype(dedifferentiation, proliferation, and redifferentiation) under certain conditions. In addition, it has been revealed that new pancreatic beta-cells are generated by neogenesis form non-beta-cells in vivo after birth.

Research Products

• [Journal Article] PGRN is a key adipokine mediating high-fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue (2012)
  • Author(s): Matsubara T, Kagawa A, Minami K, Hosooka T, Kitazawa S, Takahashi K, Tamori Y, Yokoi N, Watanabe M, Matsuo E, Nishimura O, and Seino S
  • Journal Title: Cell Metab Volume: 15(1) Pages: 38-50
• [Journal Article] PGRN is a key adipokine mediating high-fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue (2012)
  • Author(s): Matsubara T, et al
  • Journal Title: Cell Matab Volume: 15 Issue: 1 Pages: 38-50
  • DOI: 10.1016/j.cmet.2011.12.002
  • Peer Reviewed
• [Journal Article] Dynamics of insulin secretion and the clinical implications for obesity and diabetes (2011)
  • Author(s): Seino S, Shibasaki T, and Minami K
  • Journal Title: J Clin Invest Volume: 121(6) Pages: 2118-2125
• [Journal Article] In vitro generation of insulin-secreting cells from human pancreatic exocrine cells (2011)
  • Author(s): Minami K, Doi R, Kawaguchi Y, Nukaya D, Hagiwara Y, Noguchi H, Matsumoto S, and Seino S
  • Journal Title: J Diabetes Invest Volume: 2(4) Pages: 271-275
• [Journal Article] Pancreaticβ-cells are generated by neogenesis from non-β-cells after birth (2011)
  • Author(s): Nakamura K, Minami K, Tamura K, Iemoto K, Miki T, and Seino S
  • Journal Title: Biomed Res Volume: 32(2) Pages: 167-174
• [Journal Article] 膵β細胞の機能分化とインスリン分泌細胞の再生誘導 (2011)
  • Author(s): 南幸太郎
  • Journal Title: 胆と膵 Volume: 32(11) Pages: 1219-1225
• [Journal Article] Pancreatic .BETA.-cells are generated by neogenesis from non-.BETA.-cells after birth (2011)
  • Author(s): Nakamura K, et al
  • Journal Title: Biomedical Research Volume: 32 Issue: 2 Pages: 167-174
  • DOI: 10.2220/biomedres.32.167
  • NAID: 130004470777
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed
• [Journal Article] Dynamics of insulin secretion and the clinical implications for obesity and diabetes (2011)
  • Author(s): Seino S, et al
  • Journal Title: J Clinical Invest Volume: 121(invited review) Issue: 6 Pages: 2118-2125
  • DOI: 10.1172/jci45680
  • Peer Reviewed
• [Journal Article] In vitro generation of insulin-secreting cells from human pancreatic exocrine cells. (2011)
  • Author(s): Minami K, Doi R, Kawaguchi Y, Nukaya D, Hagiwara Y, Noguchi H, Matsumoto S, Seino S
  • Journal Title: J Diabetes Invest Volume: 2(掲載確定 印刷中)
  • Peer Reviewed
• [Journal Article] Tracing pancreatic β-cells by inducible Cre/loxP system. (2011)
  • Author(s): Nakamura K, Minami K, Tamura K, Iemoto K, Miki T, Seino S
  • Journal Title: Biomed Res Volume: 32(掲載確定 印刷中)
  • Peer Reviewed
• [Journal Article] Tracing phenotypic reversibility of pancreaticβ-cells in vitro (2010)
  • Author(s): Minami K, Miyawaki K, Hara M, Yamada S, and Seino S
  • Journal Title: J Diabetes Invest Volume: 1(6) Pages: 242-251
• [Journal Article] Rim2αdetermines docking and priming states in insulin granule exocytosis (2010)
  • Author(s): Yasuda T, Shibasaki T, Minami K, Takahashi H, Mizoguchi A, Uriu Y, Mori Y, Miyazaki J-i, Miki T, and Seino S
  • Journal Title: Cell Metab Volume: 12(2) Pages: 117-129
• [Journal Article] Establishment of new clonal pancreaticβ-cell lines(MIN6-K) useful for study of incretin/cAMP signaling (2010)
  • Author(s): Iwasaki M, Minami K, Shibasaki T, Miki T, Miyazaki J-I, and Seino S
  • Journal Title: J Diabetes Invest Volume: 1(4) Pages: 137-142
• [Journal Article] 膵外分泌細胞から新たな膵β細胞の誘導 (2010)
  • Author(s): 南幸太郎、清野進
  • Journal Title: Diabetes Frontier Volume: 21(4) Pages: 497-501
• [Journal Article] 膵外分泌細胞からインスリン分泌細胞の誘導 (2010)
  • Author(s): 南幸太郎、清野進
  • Journal Title: 実験医学 Volume: 28(9) Pages: 1368-1372
• [Journal Article] Establishment of new clonal pancreatic β-cell lines (MIN6-K) useful for study of incretin/cAMP signaling. (2010)
  • Author(s): Iwasaki M, Minami K, Shibasaki T, Miki T, Miyazaki J-I, Seino S
  • Journal Title: J Diabetes Invest Volume: 1 Pages: 137-142
  • Peer Reviewed
• [Journal Article] Rim2α determines docking and priming states in insulin granule exocytosis. (2010)
  • Author(s): Yasuda T, Shibasaki T, Minami K, Takahashi H, Mizoguchi A, Uriu Y, Mori Y, Miyazaki J-i, Miki T, Seino S
  • Journal Title: Cell Metab Volume: 12 Pages: 117-129
  • Peer Reviewed
• [Journal Article] Tracing phenotypic reversibility of pancreatic β-cells in vitro. (2010)
  • Author(s): Minami K, Miyawaki K, Hara M, Yamada S, Seino S
  • Journal Title: J Diabetes Invest Volume: 1 Pages: 242-251
  • Peer Reviewed
• [Journal Article] The pancreatic β-cell signaling : toward better understanding of diabetes and its treatment. (2010)
  • Author(s): Seino S, Shibasaki T, Minami K.
  • Journal Title: Proc Jpn Acad Volume: 86 Pages: 563-577
  • Peer Reviewed
• [Journal Article] Mature acinar cells are refractory to carcinoma development by targeted activation of Ras oncogene in adult rats. (2010)
  • Author(s): Tanaka H, Fukamachi K, Futakuchi M, Alexander DB, Long N, Tamamushi S, Minami K, Seino S, Ohara H, Joh T, Tsuda H
  • Journal Title: Cancer Sci 101 Pages: 341-346
  • Peer Reviewed
• [Journal Article] The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs (2009)
  • Author(s): Zhang C-L, Katoh M, Shibasaki T, Minami K, Sunaga Y, Takahashi H, Yokoi N, Iwasaki M, Miki T, and Seino S
  • Journal Title: Science Volume: 325(5940) Pages: 607-610
• [Journal Article] 膵β細胞の特性と再生インスリン分泌細胞に必要な機能 (2009)
  • Author(s): 南幸太郎、清野進
  • Journal Title: 月刊糖尿病 Volume: 1(4) Pages: 26-34
• [Journal Article] The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs. (2009)
  • Author(s): Zhang C-L, Katoh M, Shibasaki T, Minami K, Sunaga Y, Takahashi H, Yokoi N, Iwasaki M, Miki T, Seino S
  • Journal Title: Science 325 Pages: 607-610
  • Peer Reviewed
• [Journal Article] 膵β細胞の特性と再生インスリン分泌細胞に必要な機能 (2009)
  • Author(s): 南幸太郎、清野進
  • Journal Title: 月刊糖尿病 1 Pages: 26-34
• [Presentation] Development of tools for beta cell research : pancreatic beta cell lines and gene-modified animals (2011)
  • Author(s): Minami K
  • Organizer: Beta Cell Workshop 2011 : Programming Beta Cell Development, Impairment and Regeneration
  • Place of Presentation: Helsinger, Denmark
  • Year and Date: 2011-10-24
• [Presentation] Development of tools for beta cell research : pancreatic beta cell lines and gene-modified animals (2011)
  • Author(s): Minami K
  • Organizer: Beta Cell Workshop 2011 : Programming Beta Cell Development, Impairment and Regeneration
  • Place of Presentation: ヘルジンガー(デンマーク)(招待講演)
  • Year and Date: 2011-10-24
• [Presentation] Pancreatic exocrine-to-endocrine transdifferentiation in vitro (2011)
  • Author(s): Minami K
  • Organizer: Danish-Japanese Workshop "Molecular Diabetology"
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2011-10-21
• [Presentation] Self-replication is not the only mechanism of maintenance of pancreatic beta-cell mass after birth (2011)
  • Author(s): Minami K, Tamura K, Iemoto K, Nakamura K, and Seino S
  • Organizer: 47th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2011-09-13
• [Presentation] Self-replication is not the only mechanism of maintenance of pancreatic beta-cell mass after birth (2011)
  • Author(s): Minami K, et al
  • Organizer: 47th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: リスボン(ポルトガル)
  • Year and Date: 2011-09-13
• [Presentation] Elucidation of pancreaticβ-cell fate using inducible Cre/loxP system (2011)
  • Author(s): Tamura K, Minami K, Nakamura K, Iemoto K, and Seino S
  • Organizer: The 3^<rd> Asian Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Beijing, China
  • Year and Date: 2011-07-23
• [Presentation] Elucidation of pancreatic β-cell fate using inducible Cre/loxP system (2011)
  • Author(s): Tamura K, et al
  • Organizer: The 3^<rd> Asian Scientific Meeting of the Asian Associati on for the Study of Diabetes
  • Place of Presentation: 北京(中国)
  • Year and Date: 2011-07-23
• [Presentation] Induction of incretin responsiveness from incretin-unresponsive clonal beta-cells by formation of pseudoislets (2011)
  • Author(s): Aini W, et al
  • Organizer: The 3^<rd> Asian Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: 北京(中国)
  • Year and Date: 2011-07-23
• [Presentation] ヒト膵外分泌細胞からのインスリン分泌細胞の誘導 (2011)
  • Author(s): 南幸太郎、糠谷大樹、萩原慶明、清野進
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-20
• [Presentation] 誘導性Cre/loxPシステムを用いた膵β細胞の運命追跡 (2011)
  • Author(s): 田村香楠子、南幸太郎、中村維文、家本啓祐、三木隆司、清野進
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-20
• [Presentation] ヒト膵外分泌細胞からのインスリン分泌細胞の誘導 (2011)
  • Author(s): 南幸太郎, 他
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: さっぽろ芸術文化の館(北海道)
  • Year and Date: 2011-05-20
• [Presentation] 誘導性Cre/loxPシステムを用いた膵β細胞の運命追跡 (2011)
  • Author(s): 田村香楠子, 他
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: さっぽろ芸術文化の館(北海道)
  • Year and Date: 2011-05-20
• [Presentation] 新規アディポカインProgranulin (PGRN)の同定とインスリン抵抗性ならびに肥満における役割 (2011)
  • Author(s): 松原稔哉, 他
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: さっぽろ芸術文化の館(北海道)
  • Year and Date: 2011-05-20
• [Presentation] 膵β細胞のメタボローム解析 (2010)
  • Author(s): 岩崎真宏、南幸太郎、柴崎忠雄、三木隆司、宮崎純一、清野進
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 膵β細胞のメタボローム解析 (2010)
  • Author(s): 岩崎真宏、南幸太郎、柴崎忠雄、三木隆司、宮崎純一、清野進
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2010-12-10
• [Presentation] Induction of cAMP responsiveness from cAMP unresponsive β-cells by formation of pseudoislets. (2010)
  • Author(s): Iwasaki M, Minami K, Shibasaki T, Miki T, Miyazaki J-I, Seino S.
  • Organizer: 70th Scientific Sessions, American Diabetes Association
  • Place of Presentation: 米国オーランド
  • Year and Date: 2010-06-26
• [Presentation] Establishment of new clonal pancreaticβ-cell lines(MIN6-K) useful for study of incretin/cAMP signaling (2010)
  • Author(s): Iwasaki M, Minami K, Shibasaki T, Miki T, Miyazaki J-I, and Seino S
  • Organizer: The 2^<nd> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Okayama, Japan
  • Year and Date: 2010-05-28
• [Presentation] Establishment of new clonal pancreatic β-cell lines (MIN6-K) useful for study of incretin/cAMP signaling. (2010)
  • Author(s): Iwasaki M, Minami K, Shibasaki T, Miki T, Miyazaki J-I, Seino S.
  • Organizer: The 2^<nd> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: 岡山全日空ホテル(岡山県)
  • Year and Date: 2010-05-28
• [Presentation] 膵(R)細胞内代謝とインクレチンによるcAMPシグナルとの相互作用 (2010)
  • Author(s): 岩崎真宏、南幸太郎、柴崎忠雄、中山泰宗、原田和生、馬場健二、三木隆司、宮崎純一、福崎英一郎、清野進
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-27
• [Presentation] インスリン顆粒の開口放出機構におけるRim2αの役割 (2010)
  • Author(s): 安田貴雄、柴崎忠雄、三木隆司、高橋晴美、宮崎純一、南幸太郎、清野進
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-27
• [Presentation] シンポジウム「膵内分泌機能の再生～移植から再生医療まで～」:分化転換によるインスリン分泌細胞の分化誘導 (2010)
  • Author(s): 南幸太郎、清野進
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-27
• [Presentation] 分化転換によるインスリン分泌細胞の分化誘導 (2010)
  • Author(s): 南幸太郎、清野進
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)(招待講演)
  • Year and Date: 2010-05-27
• [Presentation] インスリン顆粒の開口放出機構におけるRim2αの役割 (2010)
  • Author(s): 安田貴雄、柴崎忠雄、三木隆司、高橋晴美、宮崎純一、南幸太郎、清野進
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)
  • Year and Date: 2010-05-27
• [Presentation] 膵[○!R]細胞内代謝とインクレチンによるcAMPシグナルとの相互作用 (2010)
  • Author(s): 岩崎真宏、南幸太郎、柴崎忠雄、中山泰宗、原田和生、馬場健二、三木隆司、宮崎純一、福崎英一郎、清野進
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)
  • Year and Date: 2010-05-27
• [Presentation] 新規アディポカインProgranulin(PGRN)の同定とインスリン抵抗性ならびに肥満における役割 (2010)
  • Author(s): 松原稔哉、三田綾子、南幸太郎、田守義和、北澤荘平、渡辺真、松尾英一、西村紀、清野進
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2010-05-20
• [Presentation] Tracing phenotypic reversibility of pancreatic beta-cells in vitro (2010)
  • Author(s): Minami K, Miyawaki K, Seino S
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-30
• [Presentation] Induction of cAMP responsiveness from cAMP unresponsiveβ-cells by formation of pseudoislets (2010)
  • Author(s): Iwasaki M, Minami K, Shibasaki T, Miki T, Miyazaki J-I, and Seino S
  • Organizer: 70th Scientific Sessions, American Diabetes Association
  • Place of Presentation: Orlando, USA
• [Presentation] 膵前駆細胞としてのDBA結合細胞の特性解析 (2009)
  • Author(s): 浅野優、石崎勝彦、南幸太郎、清野進
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] 膵外分泌細胞からの膵β細胞再生 (2009)
  • Author(s): 南幸太郎
  • Organizer: 第14回静岡健康・長寿フォーラム
  • Place of Presentation: 静岡
  • Year and Date: 2009-10-03
• [Presentation] 膵外分泌細胞からの膵β細胞再生 (2009)
  • Author(s): 南幸太郎
  • Organizer: 第14回静岡健康・長寿フォーラム
  • Place of Presentation: 静岡県コンベンションアーツセンター(静岡県)
  • Year and Date: 2009-10-03
• [Presentation] 膵組織前駆細胞の誘導と特性解析 (2009)
  • Author(s): 南幸太郎、萩原慶明、浅野優、石崎勝彦、清野進
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-23
• [Presentation] 膵組織前駆細胞の誘導と特性解析 (2009)
  • Author(s): 南幸太郎、萩原慶明、浅野優、石崎勝彦、清野進
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場,リーガロイヤルホテル大阪(大阪府)
  • Year and Date: 2009-05-23
• [Presentation] 膵β細胞メタボローム解析によるインスリン分泌機構の解明 (2009)
  • Author(s): 岩崎真宏、南幸太郎、柴崎忠雄、川原類、三木隆司、宮崎純一、福崎英一郎、清野進
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-22
• [Presentation] 偽膵島形成によるインクレチン作用の増強 (2009)
  • Author(s): 南幸太郎、岩崎真宏、柴崎忠雄、清野進
  • Organizer: 第3回インクレチン研究会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県)
  • Year and Date: 2009-04-25
• [Presentation] 膵腺房細胞における分化転換のシグナリングメカニズム (2009)
  • Author(s): 南幸太郎、清野進
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-23
• [Presentation] 膵腺房細胞における分化転換のシグナリングメカニズム (2009)
  • Author(s): 南幸太郎、清野進
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬県民会館,前橋商工会議所(群馬県)
  • Year and Date: 2009-04-23
• [Book] 再生膵β細胞ソースとしての膵外分泌細胞の有用性(糖尿病学2010) (2010)
  • Author(s): 南幸太郎、清野進
  • Publisher: 診断と治療社
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/phys1/
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/phys1/
• [Patent(Industrial Property Rights)] 血中インスリン抵抗性及び糖尿病マーカープログラニュリン、採血試料中のプログラニュリン濃度の分析方法、及び、インスリン抵抗性を改善及び糖尿病を改善又は抑制する物質のスクリーニング方法 (2010)
  • Inventor(s): 清野進、南幸太郎、西村紀、三田綾子、松原稔哉、渡辺真
  • Industrial Property Rights Holder: 神戸大学
  • Industrial Property Number: 2010-195871
  • Filing Date: 2010-09-01