Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes

Endocr J. 2010;57(3):211-9. doi: 10.1507/endocrj.k09e-291. Epub 2009 Dec 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 1 / virology
  • Enterovirus / genetics
  • Enterovirus / isolation & purification
  • Female
  • Humans
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Islets of Langerhans / virology
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Pancreas / immunology*
  • Pancreas / pathology
  • RNA, Viral / analysis
  • T-Lymphocytes / pathology
  • Toll-Like Receptor 3 / biosynthesis*
  • Toll-Like Receptor 7 / biosynthesis
  • Toll-Like Receptor 9 / biosynthesis


  • RNA, Viral
  • TLR3 protein, human
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9