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

Saeko SHIBASAKI; Akihisa IMAGAWA; Sisko TAURIAINEN; Morio IINO; Maarit OIKARINEN; Hitoshi ABIRU; Keiji TAMAKI; Hiroaki SEINO; Katsuhiro NISHI; Izumi TAKASE; Yoshikatsu OKADA; Sae UNO; Yuko MURASE-MISHIBA; Jungo TERASAKI; Hideichi MAKINO; Iichiro SHIMOMURA; Heikki HYöTY; Toshiaki HANAFUSA

doi:10.1507/endocrj.K09E-291

ORIGINALS

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

Saeko SHIBASAKI, Akihisa IMAGAWA, Sisko TAURIAINEN, Morio IINO, Maarit OIKARINEN, Hitoshi ABIRU, Keiji TAMAKI, Hiroaki SEINO, Katsuhiro NISHI, Izumi TAKASE, Yoshikatsu OKADA, Sae UNO, Yuko MURASE-MISHIBA, Jungo TERASAKI, Hideichi MAKINO, Iichiro SHIMOMURA, Heikki HYöTY, Toshiaki HANAFUSA

Author information

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

Keywords: Insulitis, Toll-like receptor, Enterovirus

JOURNAL FREE ACCESS

2010 Volume 57 Issue 3 Pages 211-219

DOI https://doi.org/10.1507/endocrj.K09E-291

View "Advance Publication" version (December 12, 2009).

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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.

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