Mechanism of signal integration between ATP and cAMP in pancreatic beta cells

2008 Fiscal Year Self-evaluation Report

• Project/Area Number: 18390272
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Chiba University (2007-2009); Kobe University (2006)
• Principal Investigator: MIKI Takashi Chiba University, 大学院・医学研究院, 教授 (50302568)
• Project Period (FY): 2006 – 2009
• Keywords: 糖尿病 / 膵ベータ細胞 / インスリン分泌 / cAMP / ATP

Research Abstract

ATPは生命体のエネルギー源であると共に重要な代謝シグナルとして機能し、膵β細胞ではグルコースによるインスリン分泌を引き起こす引き金として機能する。一方、cAMPは種々の生命体における普遍的な細胞内シグナルであり、膵β細胞ではインスリン分泌を著明に増強させる。グルコースによるインスリン分泌ではATPが重要な代謝シグナルとなっており、細胞内ATPの増加はATP感受性K+(KATP)チャネルを閉鎖しインスリン分泌を惹起する(Miki PNAS,1998)。しかしcAMPによるインスリン分泌増強の分子メカニズムは現在でも不明な点が多い。これまでKATPチャネルは膵β細胞におけるグルコース感知に必須と考えられていたが、申請者らはKATPチャネル欠損マウスにおいても、GLP-1の存在下では明らかなグルコース応答性インスリン分泌応答が惹起されることを見出した。そこで本研究ではGLP-1によるKATPチャネル非依存性のグルコース感知機構を解明することを目指した。

Research Products

• [Journal Article] Glucose controls cytosolic Ca2+ and insulin secretion in mouse islets lacking ATP-sensitive K+ channels owing to a knockout of the pore-forming subunit Kir6.2 (2009)
  • Author(s): Ravier MA, Nenquin M, Miki T, Seino S, Henquin JC
  • Journal Title: Endocrinology 150 Pages: 33-45
  • Peer Reviewed
• [Journal Article] Critical role of the N-termial cyclic AMP-binding domain of Epac2A in its subcellular localization and function (2009)
  • Author(s): Niimura M, Miki T, Shibasaki T, Fujimoto W, Iwanaga T, Seino S
  • Journal Title: J Cell Physiol 219 Pages: 652-658
  • Peer Reviewed
• [Journal Article] Niflumic acid-sensitive ion channels play an important role in the induction of glucose-stimulated insulin secretion by cyclic AMP in mice (2009)
  • Author(s): Fujimoto W, Miki1 T, Ogura T, Zhang M, Seino Y, Satin LS, Nakaya H, Seino S
  • Journal Title: Diabetologia 52 Pages: 863-872
  • Peer Reviewed
• [Journal Article] Intestine specific homeobox (ISX) participates in the maintenance of vitamin A metabolism by regulation of beta-carotene 15,15'-monooxygenase (bcmo1) expression (2008)
  • Author(s): Seino Y, Miki T, Kiyonari H, Abe T, Fujimoto W, Kimura K, Takeuchi A, Takahashi Y, Oiso Y, Iwanaga T, Seino S
  • Journal Title: J Biol Chem 283 Pages: 4905-4911
  • Peer Reviewed
• [Journal Article] Dmbx1 is essential in agouti-related protein action (2007)
  • Author(s): Fujimoto W, Shiuchi T, Miki T, Minokoshi Y, Takahashi Y, Takeuchi A, Kimura K, Saito M, Iwanaga T, Seino S
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 15514-15519
  • Peer Reviewed
• [Journal Article] Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP (2007)
  • Author(s): Shibasaki T, Takahashi H, Miki T, Sunaga Y, Matsumura K, Yamanaka M, Zhang C, Tamamoto A, Satoh T, MiyazakiJ-I, Seino S
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 19333-193338
  • Peer Reviewed
• [Journal Article] Spontaneous recovery from hyperglycemia by regeneration of pancreatic beta-ells in Kir6.2G132S transgenic mice (2006)
  • Author(s): Oyama K, Minami K, Ishizaki K, Fuse M, Miki T, Seino S
  • Journal Title: Diabetes 55 Pages: 1930-1938
  • Peer Reviewed
• [Journal Article] KATP channel mutation confers risk for adrenergic atrial fibrillation originating from vein of Marshall (2006)
  • Author(s): Olson TM, Alekseev AE, Moreau C, Liu, XK, Zingman, LV, Miki T, Seino S, Asirvatham SJ, Jahangir A, Terzic A
  • Journal Title: Nat Clin Pract Cardiovasc Med 4 Pages: 110-116.
  • Peer Reviewed
• [Presentation] (2008)
  • Author(s): Fujimoto, W., Miki, T., 他4名
  • Organizer: 68th Annual Meeting of the American Diabetes Association
  • Place of Presentation: San Francisco
  • Year and Date: 20080000
• [Presentation] (2007)
  • Author(s): Fujimoto, W., Miki, T. 他4名
  • Organizer: 14th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: Kyoto
  • Year and Date: 20070000
• [Presentation] (2006)
  • Author(s): Miki, T. 他5名
  • Organizer: the 20th IUBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto
  • Year and Date: 20060000
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/physiol/