Development of the treatment for fulminant type1 diabetes using the model mouse

• Project/Area Number: 21591149
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka Medical College
• Principal Investigator: HANAFUSA Toshiaki 大阪医科大学, 医学部, 教授 (60164886)
• Co-Investigator(Kenkyū-buntansha): SANO Hiroyuki 大阪医科大学, 医学部, 助教 (20556435)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 劇症1型糖尿病 / encephalomyocarditis virus / GLP-1 / マクロファージ / 膵島移植 / 膵β細胞再生 / 脂肪組織由来幹細胞 / exendin-4 / マイクロアレイ / 免疫染色 / ウイルス

Research Abstract

This study has shown that exendin-4 suppresses the onset of encephalomyocarditis virus(EMCV) induced diabetes, which is a model of fulminant type 1 diabetes. Exendin-4 markedly reducedβ cell destruction by inhibiting the infiltration of macrophages into the islets and the expression of EMCV infected macrophage derived chemical mediators, TNF-α, IL-1β and iNOS. Our study clarified that it could be an important strategy to suppress macrophage activation in the treatment of fulminant type1 diabetes.

Research Products

• [Journal Article] Class II HLA genotype in fulminant type 1 diabetes-a nationwide survey with reference to GAD antibodies (2012)
  • Author(s): Tsutsumi C, Hanafusa T, et al
  • Journal Title: J Diabetes Investigation Volume: 3 Issue: 1 Pages: 62-69
  • DOI: 10.1111/j.2040-1124.2011.00139.x
  • Peer Reviewed
• [Journal Article] Low CTLA-4 expression in CD4+helper T-cells in patients with fulminant type 1 diabetes (2011)
  • Author(s): Haseda F, Imagawa A, Murase-Mishiba Y, Sano H, Hirano-Kuwata S, Ueda H, Terasaki J, Hanafusa T.
  • Journal Title: Immunol Lett Volume: 30
  • Peer Reviewed
• [Journal Article] Low CTLA-4 expression in CD4+ helper T-Cells in patients with fulminant type 1 diabetes (2011)
  • Author(s): Haseda F, Hanafusa T, et al
  • Journal Title: Immunology Letters Volume: 139 Issue: 1-2 Pages: 80-86
  • DOI: 10.1016/j.imlet.2011.05.003
  • Peer Reviewed
• [Journal Article] Exendin-4, a glucagon-like peptide-1 receptor agonist, suppresses pancreatic β-cell destruction induced by encephalomyocarditis virus. (2011)
  • Author(s): Sano H, Hanafusa T, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 404 Pages: 756-751
  • Peer Reviewed
• [Journal Article] Exendin-4, a glucagon-like peptide-1 receptor agonist, suppresses pancreaticβ-cell destruction induced by encephalomyocarditis virus. (2010)
  • Author(s): Sano H, Terasaki J, Mishiba Y, Imagawa A, Hanafusa T.
  • Journal Title: Biochem Biophys Res Commun Volume: 21
  • Peer Reviewed
• [Journal Article] 特集:インクレチン製剤-基礎と臨床「膵島移植の際にインクレチン製剤は?」 (2010)
  • Author(s): 佐野寛行・花房俊昭
  • Journal Title: 肥満と糖尿病 Volume: Vol09-No.4 Pages: 575-579
• [Journal Article] 膵島移植の際にインクレチン製剤の投与は役立ちますか? (2010)
  • Author(s): 佐野寛行, 花房俊昭
  • Journal Title: 肥満と糖尿病 Volume: 9(4) Pages: 575-577
• [Journal Article] Endogenous insulin secretion even at a very low level contributes to the stability of blood glucose control in fulminant type 1 diabetes. (2010)
  • Author(s): Shibasaki S, Hanafusa T, et al.
  • Journal Title: J Diabetes Invest Volume: 1(6) Pages: 283-285
  • Peer Reviewed
• [Journal Article] 1型糖尿病になるのはなぜか(原因・機序) (2009)
  • Author(s): 佐野寛行花房俊昭
  • Journal Title: 糖尿病のすべて Pages: 24-28
• [Journal Article] Differential association of HLA with three subtypes of type 1 diabetes : fulminant, slowly progressive and acute-onset (2009)
  • Author(s): Kawabata K, Hanafusa T, et al.
  • Journal Title: Diabetologia 52 Pages: 2513-2521
  • Peer Reviewed
• [Journal Article] Fulminant type 1 diabetes as an important exception to the new diabetes criteria using HbA1c - response to the International Expert Committee (2009)
  • Author(s): Imagawa A, Hanafusa T
  • Journal Title: Diabetologia 52 Pages: 2464-2465
  • Peer Reviewed
• [Journal Article] ウイルス感染と1型糖尿病の関係は? (2009)
  • Author(s): 佐野寛行, 花房俊昭
  • Journal Title: 肥満と糖尿病 8 Pages: 513-514
• [Presentation] 脳心筋炎(EMC)ウイルスによって誘導される膵β細胞破壊に対するexendin-4の効果 (2011)
  • Author(s): 佐野寛行
  • Organizer: 糖尿病治療UP TO DATE
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-25
• [Presentation] 新時代の糖尿病治療 (2011)
  • Author(s): 佐野寛行
  • Organizer: 第268回臨床心臓病研修会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-19
• [Presentation] Exendin-4はEMCウイルスによる膵β細胞破壊を抑制する (2011)
  • Author(s): 佐野寛行
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 北海道札幌
  • Year and Date: 2011-05-20
• [Presentation] Exendin-4はEMCウイルスによる膵β細胞破壊を抑制する (2011)
  • Author(s): 佐野寛行、寺前純吾、長谷田文孝、堤千春、大西峰樹、三柴裕子、今川彰久、花房俊昭
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] Class II HLA Genotype in Fulminant Type 1 Diabetes (2009)
  • Author(s): Tsutsumi C, Hanafusa T, et al.
  • Organizer: 69th scientific sessions of American Diabetes Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2009-06-06
• [Book] 1型糖尿病における膵β細胞障害の分子機構 (2012)
  • Author(s): 長谷田文孝, 佐野寛行, 寺前純吾, 花房俊昭
  • Publisher: 羊土社
• [Book] 糖尿病イラストレイテッド (2012)
  • Author(s): 佐野寛行, 花房俊昭, ほか
  • Total Pages: 308
  • Publisher: 羊土社