Immunological prevention of type 1 diabetes using GAD65-encording DNA vaccine

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591056
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: University of Yamanashi
• Principal Investigator: KOBAYASHI Tetsuro University of Yamanashi, 大学院・医学工学総合研究部, 教授 (30113442)
• Co-Investigator(Kenkyū-buntansha): KANESHIGE Masahiro 山梨大学, 医学部附属病院, 助教 (20377518)
• Project Period (FY): 2008 – 2010
• Keywords: GAD65 / 1型糖尿病 / 膵島炎 / GAD抗体

Research Abstract

Preventive effect of human glutamic acid decarboxylase (GAD) 65 (GAD65) vaccination for type 1 diabetes was examined using NOD mice model. Subcutaneous electropolation of site-specific GAD65 fragments including GAD65 (1-83aa : N-GAD65), GAD65 (244-443aa : Center-GAD65) and GAD65 (443-585aa : C-GAD65) were done to 4 week female NOD mice.
Specific T cell responses to N-GAD65, Center-GAD65 and C-GAD65 were observed to respective GAD65 fragments in electropolated NOD mice. However, occurrence rate of diabetes in GAD65 vector- or empty vector- electropolated groups did not reach significant levels during 30 weeks.
Human GAD65 different from mice GAD65 may explain a failure to prevent the occurrence of diabetes by human site-specific GAD65 vaccination.

Research Products

• [Journal Article] Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism. (2010)
  • Author(s): Toyoshi Endo, Tetsuro Kobayashi.
  • Journal Title: Molecular Endocrinology 24(6) Pages: 1267-1273
  • Peer Reviewed
• [Journal Article] and the Members of the Japan Diabetes Society's Committee on Research on Type 1 Diabetes.Serum glycated albumin to haemoglobin A1C ratio can distinguish fulminant type 1 diabetes mellitus from type 2 diabetes mellitus. (2010)
  • Author(s): Masafumi Koga, Jun Murai, Hiroshi Saito, Soji Kasayama, Akihisa Imagawa, Toshiaki Hanafusa, Tetsuro Kobayashi
  • Journal Title: Ann Clin Biochem 47 Pages: 313-317
  • Peer Reviewed
• [Journal Article] on behalf of the Committee on Type 1 Diabetes, Japan Diabetes Society. Differential association of HLA with three subtypes of type 1 diabetes : fulminant, slowly progressive and acute-onset. (2009)
  • Author(s): Y. Kawabata, H. Ikegami, T.Awata, A.Imagawa, T.Maruyama, E.Kawasaki, S.Tanaka, A.Shimada, H.Osawa, T.Kobayashi, T.Hanafusa, K.Tokunaga, H.Makino
  • Journal Title: Diabetologia 52 Pages: 2513-2521
  • Peer Reviewed
• [Journal Article] Enterovirus Infection, CXC Chemokine Ligand 10 (CXCL10), and CXCR3 Circuit -A Mechanism of Accelerated Beta-Cell Failure in Fulminant Type 1 Diabetes-. (2009)
  • Author(s): Shoichiro Tanaka, Yoriko Nishida, Kaoru Aida, Taro maruyama, Akira Shimada, Masako Suzuki, Hiroki Shimura, Soichi Takizawa, Masashi Takahashi, Daiichiro Akiyama, Sayaka Arai-Yamashita, Fumihiko Furuya, Akio Kawaguchi, Masahiro Kaneshige, Ryohei Katoh, Toyoshi Endo, Tetsuro Kobayashi
  • Journal Title: Diabetes 58 Pages: 2285-2291
  • Peer Reviewed
• [Journal Article] Immunization with thyroglobulin induces Graves'-like disease in mice. (2009)
  • Author(s): Toyoshi Endo, Tetsuro Kobayashi
  • Journal Title: Journal of Endocrinology 202 Pages: 217-222
  • Peer Reviewed
• [Journal Article] Amylase alpha-2A autoantibodies :Novel Marker of Autoimmune Pancreatitis and Fulminant Type 1 Diabetes (2009)
  • Author(s): Toyoshi Endo, Soichi Takizawa, Shoichiro Tanaka, Masashi Takahashi, Hideki Fujii, Terumi Kamisawa, Tetsuro Kobayashi
  • Journal Title: Diabetes 58 Pages: 732-737
  • Peer Reviewed
• [Journal Article] HSP 10 is a new autoantigen in both autoimmune pancreatitis and fulminant type 1 diabetes. (2009)
  • Author(s): Takizawa S, Endo T, Xing Wanjia, Tanaka S, Kobayashi T.
  • Journal Title: Biochem Biophys Res Commun 386 Pages: 192-196
  • Peer Reviewed
• [Presentation] Pathlogical changes in the pancreas of fulminant type 1 diabetes and slowly progressive insulin-dependent(type1) diabetes. (2010)
  • Author(s): Tetsurou Kobayashi, Kaoru Aida, Shoichiro Tanaka
  • Organizer: The 11th International congress of the immunology of diabetes society.
  • Place of Presentation: songdo convensia, Incheon Korea
  • Year and Date: 20101031-20101103
• [Presentation] UK-Japan Workshop ~Frontiers of Diabetes Research~ ; Causes, Pathophysiology and Treatment of Type 1 Diabetes in Japan (2009)
  • Author(s): Tetsuro Kobayashi
  • Organizer: Science and Innovation Section
  • Place of Presentation: British Embassy Tokyo
  • Year and Date: 20090216-20090217
• [Presentation] Scientific Program Jakarta Diabetes Meeting 2008 ; Plenary Lecture I (2008)
  • Author(s): Tetsuro Kobayashi
  • Organizer: Immunological Aspect of Type 2 Diabetes : Pathophsiology and clinical Implication
  • Place of Presentation: Jakarta, Indonesia
  • Year and Date: 20081122-20081123
• [Presentation] A novel autoantibody against heat shock protein 10 in diabetes associated with autoimmune pancreatitis and fulminant type 1 diabetes. (2008)
  • Author(s): Souichi Takizawa, Toyoshi Endo, Shoichiro Tanaka, Masashi Takahashi, Tetsuro Kobayashi
  • Organizer: 68th Scientific Sessions.
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20080606-20080610