発症直後患者膵組織を用いた劇症1型糖尿病発症鍵分子の同定とその検証

2011 Fiscal Year Annual Research Report

• Project/Area Number: 21591184
• Research Institution: Osaka University
• Principal Investigator: 今川 彰久 大阪大学, 医学系研究科, 講師 (80373108)
• Keywords: 劇症1型糖尿病 / ウイルス / インスリン

Research Abstract

本年は、劇症1型糖尿病膵組織を用いて、ウイルス感染関連分子Xの発現を免疫組織化学的に検討した。対象は劇症1型糖尿病患者と健常対照者で、いずれもホルマリン固定パラフィン包埋した膵組織を用いた。免疫染色はこの分子に特異的な抗体を用いた酵素抗体法(ABC法)によりその発現を検討し、インスリン、グルカゴンに対する抗体を用いた蛍光二重染色法により、その局在を詳細に検討した。その結果、酵素抗体法では、劇症1型糖尿病患者において、連続切片のグルカゴン陽性細胞の位置(膵島)に一致して、この分子の陽性細胞の存在が明らかになった。健常対照者ではこの分子の膵島領域、膵外分泌領域であ発現はともに認めなかった。次に、二重染色法を用いて検討した結果、劇症1型糖尿病患者膵においては、この分子の陽性細胞の一部はインスリン陽性細胞であることが明らかになった。また、グルカゴン陽性細胞と二重陽性を示す細胞は認めなかった。
以上の結果から、劇症1型糖尿病において、膵β細胞へのウイルス感染の存在が裏付けられ、膵β細胞傷害に分子Xが関与していることが示唆された。
次に、マウス膵β細胞株MIN6を用いて、この分子の発現をPT-PCR法により検討したが、一般的な条件下では発現を認めなかった。そこで、この分子をコードする遺伝子の膵β細胞株MIN6への導入を試み、その方法を確立した。
これとは別に、劇症1型糖尿病患者膵においてTLR関連分子IRF-7,NF-kBの発現を検討した。しかし、有意な所見は得られなかった。この結果には、患者膵の保存状態、染色法などが影響していると考えられた。

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, Imagawa A, Ikegami H, Makino H, Kobayashi T, Hanafusa T
  • Journal Title: J Diabetes Invest Volume: 3 Pages: 62-9
  • DOI: 10.1111/j.2040-1124.2011.00139.x
  • Peer Reviewed
• [Journal Article] Preoperative insulin secretion ability and pancreatic parenchymal thickness as useful parameters for predicting postoperative insulin secretion in patients undergoing pancreaticoduodenectomy (2012)
  • Author(s): Yoshikawa A, Kozawa J, Okita K, Yoneda s, Okauchi Y, Uno S, Iwahashi H, Ohira T, Takiuchi D, Eguchi H, Takeda Y, Imagawa A, Shimomura I
  • Journal Title: Endocr J Volume: (in press)
  • DOI: 10.1507/endocrj.EJ11-0322
  • Peer Reviewed
• [Journal Article] Liraglutide is effective in type 2 diabetic patients with sustained endogenous insulin secretion capacity (2012)
  • Author(s): Kozawa J, Inoue K, Iwamoto R, Kurashiki Y, Okauchi Y, Kashine S, Kitamura T, Maeda N, Okita K, Iwahashi H, Funahashi T, Imagawa A, Shimomura I
  • Journal Title: J Diabetes Invest Volume: (in press)
  • DOI: 10.1111/j.2040-1124.2011.00168.x
  • Peer Reviewed
• [Journal Article] Clinical features of Japanese type 2 diabetics with insulinogenic index in normal range after treatment of glucotoxicity (2012)
  • Author(s): Iwahashi H, Akita E-F, Tokunaga A-F, Okita K, Horikawa Y, Imagawa A, Funahashi T, Shimomura I, Yamagata K
  • Journal Title: Diabetol Int Volume: (in press)
  • DOI: 10.1007/s13340-011-0046-7
  • Peer Reviewed
• [Journal Article] A case of long-standing autoimmune type 1 diabetes with common variable immunodeficiency (2012)
  • Author(s): Yamaoka M, Kitamura T, Moriyama M, Shima Y, Haseda F, Okita K, Sakaguchi Y, Iwahashi H, Hanafusa T, Funahashi T, Nagata M, Otsuki M, Imagawa A, Shimomura I
  • Journal Title: Diabetol Int Volume: (in press)
  • DOI: 10.1007/s13340-011-0049-4
  • Peer Reviewed
• [Journal Article] Insulin secretion capacity in normal glucose tolerance, impaired glucose tolerance, and diabetes in obese and non-obese Japanese subjects (2012)
  • Author(s): Iwahashi H, Okauchi Y, Ryo M, Noguchi M, Morita S, Kishida K, Okita K, Ohira T, Funahashi T, Nakamura T, Imasawa A, Shimomura I
  • Journal Title: J Diabetes Invest Volume: (in press)
  • DOI: 10.1111/j.2040-1124.2011.00180.x
  • Peer Reviewed
• [Journal Article] Glycated albumin to glycated hemoglobin ratio is a sensitive indicator of blood glucose variability in patients with fulminant Type 1 diabetes (2012)
  • Author(s): Matsumoto H, Murase-Mishiba Y, Yamamoto N, Sugitatsu-Nakatsukasa S, Shibasaki S, Sano H, Terasaki J, Imagawa A, Hanafusa T
  • Journal Title: Internal Med Volume: (in press)
  • Peer Reviewed
• [Journal Article] Fulminant type 1 diabetes-an important subtype in East Asia (2011)
  • Author(s): Imagawa A, Hanafusa T.
  • Journal Title: Diabetes Metab Res Rev Volume: 27 Pages: 959-64
  • Peer Reviewed
• [Journal Article] Cellular Hypoxia of Pancreatic {beta}-Cells Due to High Levels of Oxygen Consumption for Insulin Secretion in Vitro (2011)
  • Author(s): Sato Y, Endo H, Okuyama H, Takeda T, Iwahashi H, Imagawa A, Yamagata K, Shimomura I, Inoue M
  • Journal Title: J Biol Chem Volume: 286 Pages: 12524-32
  • DOI: 10.1074/jbc.M110.194738
  • Peer Reviewed
• [Journal Article] Predictors of deterioration of glucose tolerance and effects of lifestyle intervention aimed at reducing visceral fat in normal glucose tolerance subjects with abdominal obesity (2011)
  • Author(s): Akita-Fukuda E, Iwahashi H, Okauchi Y, Okita K, Noguchi M, Ogawa T, Ryo M, Kishida K, Funahashi T, Nakamura T, Matsuzawa Y, Imagawa A, Shimomura I
  • Journal Title: J Diabetes Invest Volume: 2 Pages: 218-24
  • DOI: 10.1186/1743-7075-8-57
  • 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: 139 Pages: 80-6
  • DOI: 10.1016/j.imlet.2011.05.003
  • Peer Reviewed
• [Journal Article] Type 1 Diabetes and Interferon Therapy : A nationwide survey in Japan (2011)
  • Author(s): Nakamura K, Kawasaki E, Imagawa A, Awata T, Ikegami H, Uchigata Y, Kobayashi T, Shimada A, Nakanishi K, Makino H,Maruyama T, Hanafusa T, the Research Committee on Type 1 Diabetes of the Japan Diabetes Society
  • Journal Title: Diabetes Care Volume: 34 Pages: 2084-9
  • DOI: 10.2337/dc10-2274
  • Peer Reviewed
• [Journal Article] Health Education "Hokenshido" Program Reduced Metabolic Syndrome in the Amagasaki Visceral Fat Study. Three-Year Follow-up study of 3,174 Japanese Employees (2011)
  • Author(s): Ryo M, Nakamura T, Funahashi T, Noguchi M, Kishida K, Okauchi Y, Nishizawa H, Ogawa T, Kojima S, Ohira T, Okita K, Iwahashi H, Imagawa A, Maysuawa Y, Shimomura I
  • Journal Title: Intern Med Volume: 50 Pages: 1643-8
  • DOI: 10.2169/internalmedicine.50.5039
  • Peer Reviewed
• [Journal Article] Arterial Stimulation and Venous Sampling for Glucagonomas of the Pancreas (2011)
  • Author(s): Eguchi H, Tanemura M, Marubashi S, Kobayashi S, Wada H, Okita K, Iwahashi H, Imagawa A, Shimomura I, Osuga K, Umeshita K, Wakasa K, Mori M, Doki Y, Nagano H
  • Journal Title: Hepatogastroenterology Volume: 59 Pages: 276-9
  • DOI: 10.5754/hge11392
  • Peer Reviewed
• [Journal Article] Cross-sectional and longitudinal study of association between circulating thiobarbituric acid-reacting substance levels and clinicobiochemical parameters in 1,178 middle-aged Japanese men-the Amagasaki Visceral Fat Study (2011)
  • Author(s): Okauchi Y, Kishida K, Funahashi T, Noguchi M, Ogawa T, Okita K, Iwahashi H, Ohira T, Imagawa A, Nakamura T, Shimomura I
  • Journal Title: Nutr Metab (Lond) Volume: 8 Pages: 82
  • DOI: 10.1186/1743-7075-8-82
  • Peer Reviewed
• [Journal Article] Fulminant Type 1 Diabetes-Is it Virus-Induced Diabetes? (2011)
  • Author(s): Imagawa A
  • Journal Title: J Med Virol Volume: 83 Pages: 1675
  • DOI: 10.1002/jmv.22060
  • Peer Reviewed
• [Journal Article] Right-sided acute suppurative thyroiditis caused by infectious endocarditis (2011)
  • Author(s): Inoue K, Kozawa J, Funahashi T, Nakata Y, Mitsui E, Kitamura T, Maeda N, Kishida,K, Otsuki M, Okita K, Iwahashi H, Imagawa A, Shimomura I
  • Journal Title: Intern Med Volume: 50 Pages: 2893-7
  • DOI: 10.2169/internalmedicine.50.5790
  • Peer Reviewed
• [Journal Article] Short-term effects of liraglutide on visceral fat adiposity, appetite, and food preference : a pilot study of obese Japanese patients with type 2 diabetes (2011)
  • Author(s): Inoue K, Maeda N, Kashine S, Fujishima Y, Kozawa J, Hiuge-Shimizu A, Okita K, Imagawa A, Funahashi T, Shimomura I
  • Journal Title: Cardiovasc Diabetol Volume: 10 Pages: 109
  • DOI: 10.1186/1475-2840-10-109
  • Peer Reviewed
• [Presentation] Symposium "Type 1 diabetes in East Asia" Fulminant type 1 diabetes (2011)
  • Author(s): Imagawa A
  • Organizer: 16th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2011-10-21
• [Presentation] Symposium "Type 1 diabetes" Fulminant type 1 diabetes-is it aunique Asian Phenomenon? (2011)
  • Author(s): Imagawa A
  • Organizer: The 3^<rd> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Beijing, China
  • Year and Date: 2011-07-23
• [Presentation] シンポジウム「1型糖尿病の成因と予防:新しい展開と洞察」1型糖尿病における膵ss細胞傷害機構 (2011)
  • Author(s): 今川彰久
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-20