Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes [Review]
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- Tanaka Shoichiro
- Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan
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- Aida Kaoru
- Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan
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- Nishida Yoriko
- Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan
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- Kobayashi Tetsuro
- Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan
Bibliographic Information
- Other Title
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- Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes
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Abstract
Fulminant type 1 diabetes is characterized by a rapid onset of severe hyperglycemia and ketoacidosis, with subsequent poor prognosis of diabetic complications. This review summarizes new findings related to the pathophysiology of accelerated β-cell failure in fulminant type 1 diabetes. Immunohistological examination revealed the presence of enterovirus in pancreatic islet cells and exocrine tissues and hyperexpression of pattern recognition receptors (PRRs) including melanoma differentiation-associated antigen 5 (MDA5), retinoic acid-inducible gene-I (RIG-I), Toll-like receptor (TLR)3 and TLR4, essential sensors of innate immunity, in islet cells and mononuclear cells (MNCs) infiltrating islets. Interferon (IFN)-α and IFN-β, products of PRR cascades, were expressed in both islet cells and infiltrating MNCs. Phenotypes of infiltrating cells around and/or into islets were mainly dendritic cells, macrophages and CD8+ T cells. Islet β-cells simultaneously expressed CXC chemokine ligand 10 (CXCL10), IFN-γ and interleukin-18, indicating that these chemokines/ cytotoxic cytokines mutually amplify their cytoplasmic expression in the islet cells. These positive feedback systems might enhance adaptive immunity, leading to rapid and complete loss of β-cells in fulminant type 1 diabetes. In innate and adaptive/autoimmune immune processes, the mechanisms behind bystander activation/killing might further amplify β-cell destruction. In addition to intrinsic pathway of cell apoptosis, the Fas and Fas ligand pathway are also involved as an extrinsic pathway of cell apoptosis. A high prevalence of anti-amylase autoantibodies was recognized in patients with fulminant type 1 diabetes, which suggests that Th2 T-cell reactive immunity against amylase might contribute to β-cell destruction in fulminant type 1 diabetes.
Journal
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- Endocrine Journal
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Endocrine Journal 60 (7), 837-845, 2013
The Japan Endocrine Society
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Details 詳細情報について
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- CRID
- 1390001206297265408
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- NII Article ID
- 10031195751
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- NII Book ID
- AA10901436
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- COI
- 1:STN:280:DC%2BC3sjjtFKrsQ%3D%3D
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- ISSN
- 13484540
- 09188959
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- PubMed
- 23774118
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed