Expression of Toll-like Receptors in the Pancreas of Recent-onset Fulminant Type 1 Diabetes

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  • SHIBASAKI Saeko
    First Department of Internal Medicine, Osaka Medical College, Japan
  • IMAGAWA Akihisa
    First Department of Internal Medicine, Osaka Medical College, Japan Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Japan
  • TAURIAINEN Sisko
    Department of Virology, Medical School, University of Tampere, Tampere, Finland
  • IINO Morio
    Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • OIKARINEN Maarit
    Department of Virology, Medical School, University of Tampere, Tampere, Finland
  • ABIRU Hitoshi
    Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • TAMAKI Keiji
    Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • SEINO Hiroaki
    Diabetic Center, Ota-Nisinouchi Hospital, Japan
  • NISHI Katsuhiro
    Department of Legal Medicine, Shiga University of Medical Science, Japan
  • TAKASE Izumi
    Department of Legal Medicine, Shiga University of Medical Science, Japan
  • OKADA Yoshikatsu
    Department of Pathology, Osaka Medical College, Japan
  • UNO Sae
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Japan
  • MURASE-MISHIBA Yuko
    First Department of Internal Medicine, Osaka Medical College, Japan
  • TERASAKI Jungo
    First Department of Internal Medicine, Osaka Medical College, Japan
  • MAKINO Hideichi
    Diabetes Research Center, Takanoko Hospital, Japan
  • SHIMOMURA Iichiro
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Japan
  • HYöTY Heikki
    Department of Virology, Medical School, University of Tampere, Tampere, Finland Department of Microbiology, Center for Laboratory Medicine, Tampere University Hospital, Tampere, Finland
  • HANAFUSA Toshiaki
    First Department of Internal Medicine, Osaka Medical College, Japan

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Abstract

Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ-hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256 % while that of normal control was 1.745 %. Macrophages and T cells-but no natural killer cells-had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6 % of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7± 7.0 % of T cells and 62.7± 32.3 % of macrophages (mean± SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. Enterovirus RNA was detected in beta-cell positive islets in one of the three patients by in situ-hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.

Journal

  • Endocrine Journal

    Endocrine Journal 57 (3), 211-219, 2010

    The Japan Endocrine Society

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