Functional analysis of pancreatic beta-cells in metabolic disorders using the fluorescent ATP probe gene transgenic mouse

• Project/Area Number: 25461346
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: NAGASHIMA KAZUAKI 京都大学, 医学(系)研究科(研究院), 講師 (40324628)
• Co-Investigator(Kenkyū-buntansha): IMAMURA HIROMI 京都大学, 生命科学研究科, 准教授 (20422545)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ATP / KATPチャネル / 糖代謝異常

Outline of Final Research Achievements

To visualize and analyze intracellular ATP dynamics in physiological condition, we generated a series of fluorescence resonance energy transfer (FRET)-based indicators for ATP. Using the fluorescent ATP probe, the fluorescent Ca2+ probe, and the transgenic mouse expressing ATP probe protein in pancreatic beta-cells, we carried out several functional analyses of intracellular ATP and Ca2+ concentrations in living pancreatic beta-cells.

Research Products

• [Int'l Joint Research] ロズウェルパーク癌研究所(米国)
• [Int'l Joint Research] マンチェスター大学/マンチェスターロイヤル診療所(英国)
• [Journal Article] Src regulates insulin secretion and glucose metabolism by influencing subcellular localization of glucokinase in pancreatic β-cells. (2016)
  • Author(s): Sato H, Nagashima K, Ogura M, Sato Y, Tahara Y, Ogura K, Yamano G, Sugizaki K, Fujita N, Tatsuoka H, Usui R, Mukai E, Fujimoto S, Inagaki N.
  • Journal Title: Journal of Diabetes Investigation Volume: 7 Issue: 2 Pages: 171-178
  • DOI: 10.1111/jdi.12407
  • NAID: 120005770743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β cell mass via epigenetic modification of Cdkn1c. (2015)
  • Author(s): Asahara S, Etoh H, Inoue H, Teruyama K, Shibutani Y, Ihara Y, Kawada Y, Bartolome A, Hashimoto N, Matsuda T, Koyanagi-Kimura M, Kanno A, Hirota Y, Hosooka T, Nagashima K, Nishimura W, Inoue H, Matsumoto M, Higgins MJ, Yasuda K, Inagaki N, Seino S, Kasuga M, Kido Y.
  • Journal Title: Proceedings of the National Acaddemy of Scienceof the United States of America Volume: 112(27) Issue: 27 Pages: 8332-8337
  • DOI: 10.1073/pnas.1422104112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The plasma membrane calcium pump in pancreatic cancer cells exhibiting the Warburg effect relies on glycolytic ATP (2015)
  • Author(s): James AD, Patel W, Butt Z, Adiamah M, Dakhel R, Latif A, Uggenti C, Swanton E, Imamura H, Siriwardena AK, Bruce JI
  • Journal Title: J. Bio. Chem. Volume: 290 Issue: 41 Pages: 24760-24771
  • DOI: 10.1074/jbc.m115.668707
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mitochondrial dysfunction in primary human fibroblasts triggers an adaptive cell survival program that requires AMPK-α (2015)
  • Author(s): Distelmaier F, Valsecchi F, Liemburg-Apers DC, Lebiedzinska M, Rodenburg RJ, Heil S, Keijer J, Fransen J, Imamura H, Danhauser K, Seibt A, Viollet B, Gellerich FN, Smeitink JA, Wieckowski MR, Willems PH, Koopman WJ
  • Journal Title: Biochim Biophys Acta Volume: 1852 Issue: 3 Pages: 529-540
  • DOI: 10.1016/j.bbadis.2014.12.012
  • Peer Reviewed
• [Journal Article] インスリン分泌機構とその破綻 (2015)
  • Author(s): 長嶋 一昭、稲垣 暢也
  • Journal Title: 医学のあゆみ Volume: 252 Pages: 377-382
• [Journal Article] BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked exocytosis (2014)
  • Author(s): Beguin P, Nagashima K, Mahalakshmi RN, Vigot R, Matsunaga A, Miki T, Ng MY, Ng YJ, Lim CH, Tay HS, Hwang LA, Firsov D, Tang BL, Inagaki N, Mori Y, Seino S, Launey T, Hunziker W
  • Journal Title: J Cell Biol Volume: 205 Issue: 2 Pages: 233-249
  • DOI: 10.1083/jcb.201304101
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2. (2014)
  • Author(s): Shintani Y, Drexler HC, Kioka H, Terracciano CM, Coppen SR, Imamura H, Akao M, Nakai J, Wheeler AP, Higo S, Nakayama H, Takashima S, Yashiro K, Suzuki K.
  • Journal Title: EMBO Reports Volume: 15 Issue: 4 Pages: 438-445
  • DOI: 10.1002/embr.201337945
  • Peer Reviewed / Open Access
• [Journal Article] 細胞内のATPがみたいーライブイメージングで明らかになってきた細胞内ATP濃度の時空間動態 (2014)
  • Author(s): 今村博臣
  • Journal Title: 実験医学 Volume: 32 Pages: 2515-2517
• [Journal Article] 生細胞内ATP濃度イメージング (2014)
  • Author(s): 今村博臣
  • Journal Title: 生体の科学 Volume: 65 Pages: 294-298
• [Journal Article] Palmitate induces reactive oxygen species production andβ-cell dysfunction by activating NADPH oxidase via Src signaling (2014)
  • Author(s): Sato Y, Fujimoto S, Mukai E, Sato H, Tahara Y, Ogura K, Yamano G, Ogura M, Nagashima K, Inagaki N
  • Journal Title: J Diabetes Investig Volume: 5 Issue: 1 Pages: 19-26
  • DOI: 10.1111/jdi.12124
  • Peer Reviewed
• [Journal Article] Glucose-stimulated single pancreatic islets sustain increased cytosolic ATP levels during initial Ca2+ influx and subsequent Ca2+ oscillations (2013)
  • Author(s): Tanaka T, Nagashima K, Inagaki N, Kioka H, Takashima S, Fukuoka H, Noji H, Kakizuka A and Imamura H
  • Journal Title: J Biol Chem Volume: 289 Issue: 4 Pages: 2205-2216
  • DOI: 10.1074/jbc.m113.499111
  • NAID: 120005689188
  • Peer Reviewed
• [Journal Article] Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction (2013)
  • Author(s): Sasaki M, Fujimoto S, Sato Y, Nishi Y, Mukai E, Yamano G, Sato H, Tahara Y, Ogura K, Nagashima K, Inagaki N
  • Journal Title: Diabetes Volume: 62 Issue: 6 Pages: 1996-2003
  • DOI: 10.2337/db12-0903
  • Peer Reviewed
• [Presentation] 糖尿病治療における経口血糖降下薬の最近の進歩 (2014)
  • Author(s): 長嶋一昭
  • Organizer: 京都府医師会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-15
  • Invited
• [Presentation] 新生児糖尿病の発症原因遺伝子と機能解析 (2014)
  • Author(s): 長嶋一昭
  • Organizer: 51回日本糖尿病学会近畿地方会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-25
  • Invited
• [Presentation] 細胞エネルギーを可視化する (2014)
  • Author(s): 今村博臣
  • Organizer: 第23回日本バイオイメージング学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-09-04 – 2014-09-06
  • Invited
• [Presentation] Fluorescent imaging of ATP levels in live cells. (2014)
  • Author(s): Imamura H
  • Organizer: 京都大学－台湾大学シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2014-09-01 – 2014-09-02
• [Presentation] Chronic Administration of Apple Procyanidins Ameliorate Insulin Resistance through the suppression of inflammation in Diabetic ob/ob Mice. (2014)
  • Author(s): Ogura K, Nagashima K, Shoji T, Sato Y, Tahara Y, Yamano G, Sato H, Sugizaki K, Fujita N, Ogura M, Mukai E, Fujimoto S, Inagaki N.
  • Organizer: American Diabetes Association(ADA) 72nd Scientific Sessions (ADA)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] 蛍光ATPバイオセンサーを用いたインスリン分泌細胞内ATPのダイナミクスの計測 (2013)
  • Author(s): 田中 喬, 長嶋 一昭, 稲垣 暢也, 野地 博行, 垣塚 彰, 今村 博臣.
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 神奈川県
• [Presentation] 蛍光ATPバイオセンサーを用いたATP代謝の解析 (2013)
  • Author(s): 今村博臣
  • Organizer: 第50回日本臨床分子医学会学術集会
  • Place of Presentation: 東京