Elucidation of the control structure of immunity and the onset prevention by the type 1 diabetes mellitus gene analysis

• Project/Area Number: 25461368
• 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: HIROMINE Yoshihisa 近畿大学, 医学部, 講師 (30460851)
• Co-Investigator(Kenkyū-buntansha): IKEGAMI Hiroshi 近畿大学, 医学部, 教授 (20221062) ; 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: １型糖尿病 / 膵島自己免疫 / 臓器特異性 / トランスジェニックマウス / 濃厚発症家系 / 全エクソーム解析 / 全ゲノム解析 / 臓器特異的自己免疫疾患 / 関連解析 / コンジェニックマウス

Outline of Final Research Achievements

Type 1 diabetes mellitus is the organ-specific autoimmune disease that β cell in pancreatic islets is destroyed by immune mechanism and to clarify the mechanism of immunoregulation leads to treatment of type 1 diabetes mellitus.
To clarify the immunoregulation in the type 1 diabetes mellitus, we identify new genes susceptibility to type 1 diabetes mellitus and analyze correlation between autoimmune diseases in different organs.
As a result, we clarified intergenic correlation between autoimmune genes.Then, we established the Mafa(which is the new genes susceptibility to type 1 diabetes mellitus) knockout NOD mouse, it was revealed that the Mafa gene affected the diabetes onset and insulitis.

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, Oiso N, Kawada A, Suzuki T, Kawabata Y, Ikegami H
  • Journal Title: J Clin Endocrinol Metab Volume: 100 Issue: 5 Pages: 1976-1983
  • DOI: 10.1210/jc.2014-3985
  • Peer Reviewed / Open Access / Int'l Joint Research / 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] Diagnostic criteria for slowly progressive insulin-dependent (type 1) diabetes ellitus (SPIDDM) (2012): report by the Committee on Slowly Progressive Insulin-Dependent (Type 1) Diabetes Mellitus of the Japan Diabetes Society. (2015)
  • Author(s): Tanaka S, Ohmori M, Awata T, Simada A, Mrrao S, Maruyama T, Kamoi K, Kawasaki E, Nakanishi K, Nagata M, Fujii S, Ikegami H, Imagawa A, Uchigata Y, Okubo M, Osawa H, Kajio H, Kawaguchi A, Kawabata Y, Satoh J, Shimizu I, Takahashi K, Makino H, Iwahashi H, Mirra J, Yasuda K, Hanafusa T, Kobayashi T
  • Journal Title: Diabetol Int Volume: 6 Issue: 1 Pages: 1-7
  • DOI: 10.1007/s13340-014-0199-2
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] 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] 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: Endocr J Volume: 60 Pages: 261-74
  • NAID: 10031170610
  • 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
• [Presentation] １型糖尿病「私たちの小児科と内科医の連携」 (2016)
  • Author(s): 池上博司
  • Organizer: 第50回糖尿病学の進歩
  • Place of Presentation: 東京（東京国際フォーラム）
  • Year and Date: 2016-02-20
  • Invited
• [Presentation] １型糖尿病と膵性糖尿病の比較：糖質インスリン比に関する検討 (2015)
  • Author(s): 安武紗良、廣峰義久、能宗伸輔、馬場谷成、伊藤裕進、川畑由美子、池上博司
  • Organizer: 第52回日本糖尿病学会近畿地方会
  • Place of Presentation: 京都（国立京都国際会館）
  • Year and Date: 2015-11-14
• [Presentation] １型糖尿病の遺伝子研究の展望「１型糖尿病の遺伝解析：遺伝子と機能」 (2015)
  • Author(s): 池上博司、能宗伸輔、川畑由美子
  • Organizer: 第13回１型糖尿病研究会
  • Place of Presentation: 東京（TKPガーデンシティPREMIUM神保町）
  • Year and Date: 2015-11-01
• [Presentation] 同胞と母に１型糖尿病を発症した１家系 (2015)
  • Author(s): 伊奈雄二郎、平田由起、田中和子、市野巧、真弓武仁、川畑由美子、池上博司、関口直孝
  • Organizer: 第13回１型糖尿病研究会
  • Place of Presentation: 東京（TKPガーデンシティPREMIUM神保町）
  • Year and Date: 2015-10-31
• [Presentation] バセドウ病と円形脱毛症における遺伝素因の共通性に関する検討 (2015)
  • Author(s): 武友保憲、能宗伸輔、馬場谷成、廣峰義久、伊藤裕進、貫戸幸星、鈴木民男、大磯直毅、川田暁、川畑由美子、池上博司
  • Organizer: 第65回日本体質医学会総会
  • Place of Presentation: 札幌（札幌コンベンションセンター）
  • Year and Date: 2015-07-05
• [Presentation] １型糖尿病の遺伝：common variantからrare variantまで (2015)
  • Author(s): 川畑由美子、能宗伸輔、池上博司
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関（ぱしふぃっくびぃなす）
  • Year and Date: 2015-05-23
  • Invited
• [Presentation] 自己免疫性１型糖尿病における内因性インスリン分泌能を規定する臨床指標および遺伝因子の解明 (2015)
  • Author(s): 武友保憲、能宗伸輔、馬場谷成、廣峰義久、原田剛史、伊藤裕進、貫戸幸星、末吉功治、吉田左和、庭野史丸、安武紗良、川畑由美子、池上博司
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関（シーモールホール）
  • Year and Date: 2015-05-22
• [Presentation] 自己免疫性1型糖尿病の遺伝子解析：β細胞機能廃絶に関わる遺伝素因の解明 (2015)
  • Author(s): 武友保憲、能宗伸輔、馬場谷成、廣峰義久、伊藤裕進、原田剛史、貫戸幸星、川畑由美子、池上博司
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: 東京（ホテルニューオータニ東京）
  • Year and Date: 2015-04-24
• [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 K, Ikegami H
  • Organizer: 1.Immunology of Diabetes Society, 14th International Congress
  • Place of Presentation: Munich, Germany（Hilton Munich Park）
  • Year and Date: 2015-04-13
  • Int'l Joint Research
• [Presentation] A case of mixed cortical-medullary tumor accompanied with unilateral multiple micronodules producing aldosterone (2014)
  • Author(s): Ito H, Kawabata Y, Yoshida S, Kanto K, Taketomo Y, Hiromine Y, Babaya N, Noso S, Sasano H, Hiroshi Ikegami
  • Organizer: International Symposium on Pheochromocytoma and Paraganglioma, 2014
  • Place of Presentation: Kyoto, Japan(Mielparque Kyoto)
  • Year and Date: 2014-09-17 – 2014-09-20
• [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] 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 Session of America Diabetes Association
  • Place of Presentation: Chicago, USA
• [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, Choongyong Park, Taketomo Y, Ikegami H
  • Organizer: 13th International Congress of the Immunology of Diabetes
  • 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
  • Place of Presentation: Lorne, Australia
• [Book] 糖尿病 最新の治療 2016-2018 (2016)
  • Author(s): 廣峰義久、池上博司
  • Total Pages: 5
  • Publisher: 南江堂
• [Book] 新時代の臨床糖尿病学（上）よりよい血糖管理をめざして (2016)
  • Author(s): 廣峰義久、池上博司
  • Total Pages: 5
  • Publisher: 日本臨床社
• [Book] 糖尿病学 (2015)
  • Author(s): 能宗伸輔、池上博司
  • Total Pages: 11
  • Publisher: 西村書店
• [Book] 月刊糖尿病7 (2015)
  • Author(s): 馬場谷成、池上博司
  • Total Pages: 9
  • Publisher: 医学出版
• [Book] 糖尿病のすべて 成因研究update (2015)
  • Author(s): 廣峰義久、池上博司
  • Total Pages: 5
  • Publisher: 医学のあゆみ
• [Book] 最新医学 3月増刊号 (2015)
  • Author(s): 能宗伸輔、池上博司
  • Total Pages: 9
  • Publisher: 最新医学社
• [Book] 糖尿病治療のニューパラダイム第1巻 (2014)
  • Author(s): 廣峰義久、池上博司
  • Total Pages: 9
  • Publisher: 医薬ジャーナル社
• [Book] 糖尿病 UP・DATE 賢島セミナー 糖尿病療養のイノベーション (2013)
  • Author(s): 池上博司
  • Total Pages: 8
  • Publisher: 時事通信社
• [Book] 糖尿病の疾患感受性遺伝子Update (2013)
  • Author(s): 廣峰義久、池上博司
  • Total Pages: 6
  • Publisher: 医学のあゆみ