Functional regulation of pancreatic islets by cell to cell communication

• Project/Area Number: 25461330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Chiba University
• Principal Investigator: MUKAI ERI 千葉大学, 医学(系)研究科(研究院), 講師 (60362539)
• Co-Investigator(Kenkyū-buntansha): MIKI Takashi 千葉大学, 大学院医学研究院, 教授 (50302568)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞間情報伝達 / インスリン分泌 / 糖代謝

Outline of Final Research Achievements

Pancreatic beta cells form islets of Langerhans and the feature is needed for integrated insulin secretory responses. We hypothesized that gap junction between neighboring beta cells plays a role in the integrated secretory regulation and studied the mechanism of signal transduction through gap junction. By construction of analysis tools of signal transduction between beta cells, propagation of signal transduction to neighboring cells could be detected. The propagation was not strong and lasting like cardiac myocytes. Connexin 36 was shown to be responsible for secretory function, but the inhibition of its expression by present experimental system seems to be weak. Therefore, new system for regulation of the expression are needed for analysis of gap junction.

Research Products

• [Journal Article] Distinct effects of dipeptidyl peptidase-4 inhibitor and glucagon-like peptide-1 receptor agonist on islet morphology and function. (2016)
  • Author(s): Morita A, Mukai E, Hiratsuka A, Takatani T, Iwanaga T, Lee EY, Miki T.
  • Journal Title: Endocrine Volume: 51 Issue: 3 Pages: 429-439
  • DOI: 10.1007/s12020-015-0733-4
  • Peer Reviewed / Acknowledgement Compliant
• [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] Synthesis and evaluation of 18F-labeled mitiglinide derivatives as positron emission tomography tracers for β-cell imaging. (2014)
  • Author(s): H Kimura, H Matsuda H Fujimoto, K Arimitsu, K Toyoda, E Mukai, H Nakamura, Y Ogawa, M Takagi, Mo Ono, N Inagaki, H Saji.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 22 Issue: 13 Pages: 3270-3278
  • DOI: 10.1016/j.bmc.2014.04.059
  • NAID: 120005456028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enhanced vascular endothelial growth factor signaling in islets contributes to β cell injury and consequential diabetes in Spontaneously Diabetic Torii rats. (2014)
  • Author(s): Mukai E, Ohta T, Kawamura H, Lee EY, Morita A, Sasase T, Miyajima K, Inagaki N, Iwanaga T, Miki T.
  • Journal Title: Diabetes Res Clin Pract Volume: 106 Issue: 2 Pages: 303-311
  • DOI: 10.1016/j.diabres.2014.08.023
  • Peer Reviewed / Acknowledgement Compliant
• [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] 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] DPP-4阻害薬とGLP-1受容体作動薬の膵β細胞量制御の違い－膵β細胞傷害/再生マウスによる検討－ (2015)
  • Author(s): 向英里、森田亜州華、平塚綾乃、高谷具純、李恩瑛、三木隆司
  • Organizer: 第29回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 京都大学芝蘭会館（京都府・京都市）
  • Year and Date: 2015-02-13 – 2015-02-14
• [Presentation] Dual roles of a DPP-4 inhibitor on cytoprotection and proliferation of pancreatic β-cells in a mouse model of β-cell injury/regeneration. (2014)
  • Author(s): E Mukai, A Morita, A Hiratsuka, T Takatani, EY Lee, T Miki.
  • Organizer: 50th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Vienna (Austria)
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] Chronic Administration of Apple Procyanidins Ameliorate Insulin Resistance through the Suppression of Inflammation in Diabetic ob/ob Mice. (2014)
  • Author(s): K Ogura, K Nagashima, T Shoji, Y Sato, Y Tahara, G Yamano, H Sato, K Sugizaki, N Fujita, M Ogura, E Mukai, S Fujimoto, N Inagaki.
  • Organizer: 74th Scientific Sessions of American Diabetes Association
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] DPP-IV阻害薬による膵β細胞死抑制と増殖促進-膵β細胞傷害/再生マウスを用いた検討 (2014)
  • Author(s): 森田亜州華、向英里、平塚文乃、高谷具純、李恩瑛、三木隆司
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 林檎由来プロシアニジン類長期投与によるob/obマウスにおけるインスリン抵抗性改善機序の検討 (2014)
  • Author(s): 小倉かさね、長嶋一昭、庄司俊彦、佐藤雄一、田原裕美子、山野言、佐藤広規、杉崎和、藤田直尚、小倉雅仁、向英里、藤本新平、稲垣暢也
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] パルミチン酸はSrc活性化によるNADPHオキシダーゼ由来ROS産生増加を介して膵β細胞機能を低下させる (2014)
  • Author(s): 佐藤雄一、藤本新平、向英里、佐藤広規、田原裕美子、小倉かさね、山野言、杉崎和、小倉雅仁、長嶋一昭、稲垣暢也
  • Organizer: 第28回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 宮崎
• [Presentation] VEGFシグナル阻害はSDTラットにおけるb細胞傷害と糖尿病発症を抑制する (2013)
  • Author(s): 向英里、太田毅、河村治清、李恩瑛、森田亜州華、笹瀬智彦、稲垣暢也、岩永敏彦、三木隆司
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] パルミチン酸はSrc活性化を介してNADPHオキシダーゼ(NOX)由来の活性酸素種(ROS)産生を増加させて膵β細胞機能低下をもたらす (2013)
  • Author(s): 佐藤 雄一、藤本新平、向英里、佐藤広規、田原裕美子、小倉かさね、山野言、杉崎和、小倉雅仁、長嶋一昭、稲垣暢也
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Thioredoxin binding protein-2(TBP-2)が膵b細胞で果たす役割についての検討 (2013)
  • Author(s): 田原裕美子、藤本新平、杉崎和、小倉かさね、佐藤広規、山野言、佐藤雄一、向英里、小倉雅仁、長嶋一昭、稲垣暢也
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Srcはグルコキナーゼ活性調節を介して膵β細胞KATPチャネルに直接作用してインスリン分泌を惹起する (2013)
  • Author(s): 佐藤 広規、長嶋一昭、佐藤雄一、小倉雅仁、山野言、田原裕美子、小倉かさね、杉崎和、向英里、藤本新平、稲垣暢也
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] リンゴ由来プロシアニジン類による糖尿病モデルマウスにおける抗糖尿病作用の検討 (2013)
  • Author(s): 小倉かさね、長嶋一昭、庄司俊彦、佐藤雄一、田原裕美子、山野言、佐藤広規、杉崎和、小倉雅仁、向英里、藤本新平、稲垣暢也
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Role of endogenous ROS in pancreatic b-cell dysfunction. (2013)
  • Author(s): Mukai, E.
  • Organizer: 2013 International Conference on Diabetes and Metabolism & 5th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Korea, Seoul
  • Invited
• [Presentation] Palmitate indces ROS Production and β-cell dysfunction by activating NADPH oxidase via Src signaling. (2013)
  • Author(s): Sato, Y., Fujimoto, S., Mukai, E., Sato, H., Tahara, Y., Ogura, K., Yamano, G., Ogura, M., Nagashima, K., Inagaki, N.
  • Organizer: 2013 International Conference on Diabetes and Metabolism & 5th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Korea, Seoul
• [Presentation] Chronic administration of apple procyanidins ameliorate insulin resistance in diabetic ob/ob mice. (2013)
  • Author(s): Ogura, K., Nagashima, K., Shoji, T., Sato, Y., Tahara, Y., Yamano, G., Sato, H., Sugisaki, N., Fujita, N., Ogura, M., Mukai, E., Fujimoto, S., Inagaki, N.
  • Organizer: 2013 International Conference on Diabetes and Metabolism & 5th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Korea, Seoul