Organ specificity in autoimmune diseases: beta-cells and type 1 diabetes

• Project/Area Number: 24591347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kinki University
• Principal Investigator: IKEGAMI Hiroshi 近畿大学, 医学部, 教授 (20221062)
• Co-Investigator(Kenkyū-buntansha): KAWABATA Yumiko 近畿大学, 医学部, 准教授 (80423185) ; NOSO Shinsuke 近畿大学, 医学部, 講師 (90460849) ; BABAYA Naru 近畿大学, 医学部, 講師 (10449837) ; HIROMINE Yoshihisa 近畿大学, 医学部, 講師 (30460851)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: １型糖尿病 / 遺伝子 / 自己免疫 / ゲノム / 膵島 / 糖尿病

Outline of Final Research Achievements

The aim of this study was to clarify the molecular mechanisms why only beta-cells are destroyed in type 1 diabetes. Insulin-specific transcription factor, MafA, affects expression of insulin in the thymus and induction of immunological tolerance to insulin. Functional polymorphisms of MAFA were associated with type 1 diabetes. Alopecia areata, organ-specific autoimmune disease to hair follicle, was associated with autoimmune thyroid diseases, but not with type 1 diabetes, which correlated with class II HLA haplotypes susceptible or resistant to each autoimmune disease.

Research Products

• [Journal Article] Organ-specificity in autoimmune diseases: thyroid and islet autoimmunity in alopecia areata. (2015)
  • Author(s): Noso S, Park C, Babaya N, Hiromine Y, Harada T, Ito H, Taketomo Y, Kanto K, Oiso N, Kawada A, Suzuki T, Kawabata Y, Ikegami H
  • Journal Title: J Clin Endocrinol Metab Volume: Mar 3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Low PD-1 expression in peripheral CD4+ T-cells in Japanese patients with autoimmune type 1 diabetes. (2015)
  • Author(s): Fujisawa R, Haseda F, Tsutsumi C, Hiromine Y, Noso S, Kawabata Y, Mitsui S, Terasaki J, Ikegami H, Imagawa A, Hanafusa T.
  • Journal Title: Clin Exp Immunol Volume: Feb 12 Issue: 3 Pages: 452-457
  • DOI: 10.1111/cei.12603
  • Peer Reviewed / Open Access
• [Journal Article] Genetic dissection of susceptibility genes for diabetes and related phenotypes on mouse chromosome 14 by means of congenic strains. (2014)
  • Author(s): Babaya N, Ueda H, Noso S, Hiromine Y, Itoi-Babaya M, Kobayashi M, Fujisawa T, Ikegami H
  • Journal Title: BMC Genet Volume: 15 Issue: 1 Pages: 1-10
  • DOI: 10.1186/s12863-014-0093-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diagnostic criteria for acute-onset type 1 diabetes mellitus (2012): Report of the Committee of Japan Diabetes Society on the Research of Fulminant and Acute-onset Type 1 Diabetes Mellitus. (2014)
  • Author(s): Kawasaki E, Maruyama T, Imagawa A, Awata T, Ikegami H, Uchigata Y, Osawa H, Kawabata Y, Kobayashi T, Shimada A, Shimizu I, Takahashi K, Nagata M, Makino H, Hanafusa T
  • Journal Title: J Diabetes Investig Volume: 5 Issue: 1 Pages: 115-118
  • DOI: 10.1111/jdi.12119
  • NAID: 120006986708
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility (2014)
  • Author(s): DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
  • Journal Title: Nat Genet Volume: 46 Issue: 3 Pages: 234-246
  • DOI: 10.1038/ng.2897
  • Peer Reviewed / Open Access
• [Journal Article] Novel effect of ezetimibe to inhibit the development of non-alcoholic fatty liver disease in Fatty Liver Shionogi mouse (2013)
  • Author(s): Wang X
  • Journal Title: Hepatol Res Volume: 印刷中 Issue: 1 Pages: 102-13
  • DOI: 10.1111/hepr.12092
  • Peer Reviewed / Open Access
• [Journal Article] Association study of MAFA and MAFB, genes related to organ-specific autoimmunity, with susceptibility to type 1 diabetes in Japanese and Caucasian populations. (2013)
  • Author(s): Noso S, Kawabata Y, Babaya N, Hiromine Y, Kawasaki E, Awata T, Maruyama T, Sunanda B, Oiso N, Kawada A, Suzuki T, Eisenbarth GS, Ikegami H
  • Journal Title: J Genet Syndr Gene Ther Volume: 4 Issue: 11 Pages: 204-204
  • DOI: 10.4172/2157-7412.1000204
  • Peer Reviewed
• [Journal Article] A low-frequency GLIS3 variant associated with resistance to Japanese type 1 diabetes. (2013)
  • Author(s): Awata T, Yamashita H, Kurihara S, Morita-Ohkubo T, Miyashita Y, Katayama S, Kawasaki E, Tanaka S, Ikegami H, Maruyama T, Shimada A, Takahashi K, Kawabata Y, Kobayashi T, Nishida N, Mawatari Y.
  • Journal Title: Biochem Biophys Res Commun Volume: 437 Issue: 4 Pages: 521-525
  • DOI: 10.1016/j.bbrc.2013.06.102
  • Peer Reviewed
• [Journal Article] Analysis of hepatic gene expression profile in a spontaneous mouse model of type 2 diabetes under a high sucrose diet (2013)
  • Author(s): Nojima K, Sugimoto K, Ueda H, Babaya N, Ikegami H, Rakugi H
  • Journal Title: Endocrine Journal Volume: 60 Issue: 3 Pages: 261-274
  • DOI: 10.1507/endocrj.EJ12-0258
  • NAID: 10031170610
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11. (2013)
  • Author(s): Babaya N, Ueda H, Noso S, Hiromine Y, Nojima K, Itoi-Babaya M, Kobayashi M, Fujisawa T, Ikegami H
  • Journal Title: Journal of Diabetes Research Volume: 2013 Pages: 1-6
  • DOI: 10.1155/2013/608923
  • Peer Reviewed
• [Journal Article] Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians (2012)
  • Author(s): Li H, Kilpelainen TO, Liu C, et al.
  • Journal Title: Diabetologia Volume: 55 Issue: 4 Pages: 981-995
  • DOI: 10.1007/s00125-011-2370-7
  • Peer Reviewed
• [Journal Article] Report of the Committee of the Japan Diabetes Society on the Research of Fulminant and Acute-onset Type 1 diabetes Mellitus: New diagnostic criteria of fluminant ytpe 1 diabetes mellitus (2012) (2012)
  • Author(s): Imagawa A et al.
  • Journal Title: J Diabetes Invest Volume: 3 Issue: 6 Pages: 536-539
  • DOI: 10.1111/jdi.12024
  • Peer Reviewed
• [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] Prolonged hyperinsulinemia after subcutaneous injection of 2400 U regular insulin in a suicide attempt : Time course of serum insulin with frequent measurements (2012)
  • Author(s): Hiromine Y, et al
  • Journal Title: J Diabetes Invest Volume: 3 Issue: 5 Pages: 468-470
  • DOI: 10.1111/j.2040-1124.2012.00211.x
  • Peer Reviewed
• [Journal Article] Meta-analysis of genome-wide asso- ciation studies identifies eight new loci for type 2 diabetes in east Asians (2011)
  • Author(s): Cho YS, Yamauchi T, Hara K, Kadowaki T
  • Journal Title: Nature Genatics Volume: 44 Issue: 1 Pages: 67-72
  • DOI: 10.1038/ng.1019
  • Peer Reviewed
• [Presentation] Identification of genetic loci linked to type 1 diabetes susceptibility by linkage analysis with whole exome sequencing in clustered family (2015)
  • Author(s): Noso S, Kawabata Y, Babaya N, Hiromine Y, Hosomichi, Ikegami H
  • Organizer: 14th International Congress of the Immunology of Diabetes Society
  • Place of Presentation: Munich, Germany
  • Year and Date: 2015-04-13
• [Presentation] １型糖尿病の成因：遺伝子からのアプローチ (2015)
  • Author(s): 池上博司
  • Organizer: 第49回糖尿病学の進歩
  • Place of Presentation: 岡山（岡山全日空ホテル）
  • Year and Date: 2015-02-20
  • Invited
• [Presentation] １型糖尿病の成因：なぜβ細胞だけが破壊されるのか？ (2014)
  • Author(s): 池上博司
  • Organizer: 第24回臨床内分泌代謝Update
  • Place of Presentation: さいたま市（大宮ソニックシティ）
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] １型糖尿病の遺伝素因 (2014)
  • Author(s): 能宗伸輔、川畑由美子、池上博司
  • Organizer: 第51回日本糖尿病学会近畿地方会（シンポジウム）
  • Place of Presentation: 大阪（大阪国際会議場）
  • Year and Date: 2014-10-25
• [Presentation] １型糖尿病の成因：膵β細胞特異性を規定する遺伝因子の解明とその制御 (2014)
  • Author(s): 能宗伸輔、池上博司
  • Organizer: 第57回日本糖尿病学会年次学術集会（シンポジウム）
  • Place of Presentation: 大阪（リーガロイヤルホテル）
  • Year and Date: 2014-05-23
• [Presentation] Genetics and pathogenesis of beta-cell destruction in type 1 diabetes (2013)
  • Author(s): Ikegami H
  • Organizer: 26th Spring Congress of Korean Diabetes Association， 1st Korea-Japan Diabetes Forum
  • Place of Presentation: Jeju, Korea
  • Invited
• [Presentation] Mafa knockout NOD mice are protected from type 1 diabetes despite accelerated infiltration of lymphocytes into islets (2013)
  • Author(s): Noso S, Babaya N, Hiromine Y, Kawabata Y, Ikegami H
  • Organizer: 49th European Association for the Study of Diabetes Annual Meeting
  • Place of Presentation: Barcelona, Spain
• [Presentation] A search for susceptibility genes contributing to islet-specific autoimmunity in type 1 diabetes by association studies with multiple autoimmune diseases (2013)
  • Author(s): Noso S, Kawabata Y, Babaya N, Hiromine Y, Moriguchi M, Murata K, Park C, Taketomo Y, Ikegami H
  • Organizer: 13th International Congress of the Immunology of Diabetes Society
  • Place of Presentation: Lorne, Australia
• [Presentation] Low expression level of Peripheral CD4+PD-1+T-cells in Japanese Patients with Type 1A Diabetes (2013)
  • Author(s): Fujisawa R, Haseda F, Tsutsumi C, Hiromine Y, Noso S, Kawabata Y, Mitsui S, Terasaki J, Ikegami H, Imagawa A, Hanafusa T
  • Organizer: 13th International Congress of the Immunology of Diabetes Society
  • Place of Presentation: Lorne, Australia
• [Presentation] Low Expression of PD-1 in Peripheral CD4+ T-Cells in Japanese Patients with Type 1A Diabetes (2013)
  • Author(s): Fujisawa R, Haseda F, Tsutsumi C, Hiromine Y, Noso S, Kawabata Y, Mitsui S, Terasaki J, Ikegami H, Imagawa A, Hanafusa T
  • Organizer: 73rd Scientific Sessions of America Diabetes Association
  • Place of Presentation: Chicago, USA
• [Presentation] A search for susceptibility genes, contributing to islet-specific autoimmunity, in type 1 diabetes (2012)
  • Author(s): Noso S, Ikegami H
  • Organizer: 4th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto, Japan
• [Presentation] Susceptibility genes for type 2 diabetes and related phenotypes cluster on mouse (2012)
  • Author(s): Babaya N, Noso S, Hiromine Y, Ueda H, Ikegami H
  • Organizer: 48th European Association for the Study of Diabetes Annual Meeting
  • Place of Presentation: Berlin, Germany
• [Presentation] Association of a functional polymorphism MAFA Gly346Cys with susceptibility to type 1 diabetes. (2012)
  • Author(s): Noso S, Kawabata Y, Babaya N, Hiromine Y, Kawasaki E, Awata T, Maruyama T, Babu S, Eisenbarth GS, Ikegami H
  • Organizer: 12th International Conference on the Immunology of Diabetes
  • Place of Presentation: Victoria, Canada
• [Presentation] Association of PDCD-1 (programmed cell death-1) polymorphisms in Japanese (2012)
  • Author(s): Tsutsumi C, Hiromine Y, Imagawa A, Mitsui S, Noso S, Kawabata Y, Terasaki J, Ikegami H, Hanafusa T
  • Organizer: 12th International Conference on the Immunology of Diabetes
  • Place of Presentation: Victoria, Canada
• [Presentation] Genetics of type 1 diabetes: HLA and non-HLA genes
  • Author(s): Ikegami H
  • Organizer: ISPAD Science School for Physicians 2012
  • Place of Presentation: Kyoto, Japan
  • Invited