Biological significance of receptors for mild electrical currents at 0.1 ms pulse width

• Project/Area Number: 25670260
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Kumamoto University
• Principal Investigator: Kai Hirofumi 熊本大学, 大学院生命科学研究部(薬), 教授 (30194658)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 物理療法 / 糖尿病

Outline of Final Research Achievements

Electrical current at physiological strength has been applied as a therapeutic approach for various diseases. Several of our works showed that mild electrical stimulation (MES) at 0.1-ms pulse width has positive impact on organisms. But despite the growing evidence of the beneficial effects of MES, its effects on individual animals and the molecular underpinnings are poorly understood and rarely studied.we firstly and genetically demonstrated that MES exerts beneficial effects such as stress resistance and suppression of excess fat accumulation, via activation of LKB1-AMPK signaling pathway. In addition, we identified the receptor for the MES.

Research Products

• [Journal Article] Mild electrical stimulation with heat shock reduces visceral adiposity and improves metabolic abnormalities in subjects with metabolic syndrome or type 2 diabetes: Randomized crossover trials. (2014)
  • Author(s): Kondo T, Ono K, Kitano S, Matsuyama R, Goto R, Suico MA, Kawasaki S, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E
  • Journal Title: EBioMedicine Volume: 1 Issue: 1 Pages: 80-89
  • DOI: 10.1016/j.ebiom.2014.11.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mild Electrical Stimulation Increases Stress Resistance and Suppresses Fat Accumulation via Activation of LKB1-AMPK Signaling Pathway in C. elegans (2014)
  • Author(s): Shingo Matsuyama, Masataka Moriuchi, Mary Ann Suico, Shuichiro Yano, Saori Morino-Koga, Tsuyoshi Shuto, Kunitoshi Yamanaka, Tatsuya Kondo, Eiichi Araki, Hirofumi Kai
  • Journal Title: PLOS ONE Volume: 9(12): e114690 Issue: 12 Pages: e114690-e114690
  • DOI: 10.1371/journal.pone.0114690
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of heat shock response in insulin resistance and diabetes. (2014)
  • Author(s): Kondo T, Motoshima H, Igata M, Kawashima J, Matsumura T, Kai H, Araki E
  • Journal Title: Diabetes Metab J Volume: 38 Issue: 2 Pages: 100-1006
  • DOI: 10.4093/dmj.2014.38.2.100
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mild electrical stimulation with heat stimulation increase heat shock protein 70 in articular chondrocyte. (2013)
  • Author(s): Hiraoka N,Arai Y, Takahashi KA, Mazda O, Kishida T, Honjo K, Tsuchida S, Inoue H, Morino S, Suico MA, Kai H, Kubo T.
  • Journal Title: J Orthop Res. Volume: 17 Issue: 6 Pages: 894-900
  • DOI: 10.1002/jor.22307
  • Peer Reviewed
• [Journal Article] Mild electrical stimulation at 0.1-ms pulse width induces p53 protein phosphorylation and G2 arrest in human epithelial cells. (2013)
  • Author(s): Fukuda ft, Suico MA, Koyama K, Omachi K, Kai Y, Matsuyama S, Mitsutake K, Taura M, Mo rino-Koga S, Shuto T, Kai H.
  • Journal Title: Journal of Biological Chemistry Volume: 288(22) Issue: 22 Pages: 16117-16126
  • DOI: 10.1074/jbc.m112.442442
  • Peer Reviewed
• [Presentation] Chemical Medicine と Physical Medicine の併用療法の有用性 (2015)
  • Author(s): 甲斐 広文
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸学院大学（兵庫県神戸市）
  • Year and Date: 2015-03-25 – 2015-03-28
  • Invited
• [Presentation] Physical medicineの科学的エビデンス構築と有効な疾患モデル (2015)
  • Author(s): 甲斐 広文
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-03-18 – 2015-03-20
  • Invited
• [Presentation] The effect of Mild Electrical Stimulation with Heat Shock on kidney dysfunction in type 2 diabetic KKAy mice. (2014)
  • Author(s): Y. Kai, R. Fukuda, K. Omachi, Y. Okamoto, M. Suico, T. Shuto, H. Kai
  • Organizer: The 2014 ascb/ifcb Meeting
  • Place of Presentation: Philadelphia（USA）
  • Year and Date: 2014-12-06 – 2014-12-10
• [Presentation] 「Physical Medicine」の臨床的有用性とその科学的エビデンス (2014)
  • Author(s): 甲斐 広文
  • Organizer: 第22回クリニカルファーマシーシンポジウム医療薬学フォーラム2014
  • Place of Presentation: ビックサイトTFTホール（東京都江東区）
  • Year and Date: 2014-06-28 – 2014-06-29
  • Invited
• [Presentation] Low-intensity direct electrical current stress suppresses pro-inflammatory cytokines expression via inhibition of multiple signaling pathways (2013)
  • Author(s): I. Shitanda, S. Matsuyama, K. Mitsutake, R. Fukuda, Y. Kai, M. Suico, T. Shuto, H. Kai
  • Organizer: 2013 ASCB Annual Meeting
  • Place of Presentation: The New Orleans Ernest N. Morial Convention Center, New Orleans, Lousiana,USA
• [Presentation] Specific pulse-width mild electrical stimulation induces p53 activation via p38 MAPK and ameliorates LPS-induced inflammatory cytokine response (2013)
  • Author(s): R. Fukuda, K. Omachi, M. A. Suico, K. Koyama, Y. Kai, S. Matsuyama, K. Mitsutake, S. Morino-Koga, T. Shuto, H. Kai.
  • Organizer: 15th International congress of immunology
  • Place of Presentation: Mico Milano Congressi, Milano, ITALY
• [Presentation] Mild electrical stimulation with heat shock ameliorates nephritis and proteinuria in mouse model of X-linked alport syndrome (2013)
  • Author(s): Y. Kai, T. Koga, R. Fukuda, S. Morino-Koga, M. A. Suico, K. Koyama, T. Sato, T. Shuto, H. Kai
  • Organizer: 15th International congress of immunology
  • Place of Presentation: Mico Milano Congressi, Milano, ITALY
• [Presentation] Beneficial effects and their molecular mechanisms of specific pulse width mild electrical stress as physical medicine (2013)
  • Author(s): H. Kai, T. Kondo, M.A. Suico, T. Shuto, E. Araki
  • Organizer: VI International Congress on Stress Proteins in Biology and Medicine
  • Place of Presentation: Edge conference Centre, Sheffield, UK
• [Presentation] Specific pulse width mild electrical stress increases stress resistance and suppresses fat accumulation via activation of LKB1-AMPK signaling pathway. (2013)
  • Author(s): Shingo Matsuyama, Masataka Moriuchi, Mary Ann Suico, Tsuyoshi Shuto and Hirofumi Kai
  • Organizer: VI International Congress on Stress Proteins in Biology and Medicine
  • Place of Presentation: Edge conference Centre, Sheffield, UK
• [Presentation] 新たなPhysical Medicine；最適化された物理ストレスを活用した医療（予防）機器 (2013)
  • Author(s): 甲斐 広文
  • Organizer: 第11回維持透析患者の補完・代替医療研究会
  • Place of Presentation: 名古屋ルーセントタワー（愛知）
• [Remarks] 熊本大学大学院薬学教育部 遺伝子機能応用学研究室
  • URL: http://molmed730.org/index.html