Role of Macrophages in the Development of Pancreatic Islet Injury in Spontaneously Diabetic Torii Rats

• INOKUCHI Chie

  Division of Diabetes and Metabolism, Department of Internal Medicine, Hyogo College of Medicine Institute for Advanced Medical Sciences and the Department of Emergency and Disaster Medicine, Hyogo College of Medicine

• UEDA Haruyasu

  Institute for Advanced Medical Sciences and the Department of Emergency and Disaster Medicine, Hyogo College of Medicine Department of Pharmacy School of Pharmacy, Hyogo University of Health Sciences

• HAMAGUCHI Tomoya

  Division of Diabetes and Metabolism, Department of Internal Medicine, Hyogo College of Medicine

• MIYAGAWA Jun-ichiro

  Division of Diabetes and Metabolism, Department of Internal Medicine, Hyogo College of Medicine

• SHINOHARA Masami

  Planning and Development Section, CLEA Japan Inc.

• OKAMURA Haruki

  Institute for Advanced Medical Sciences and the Department of Emergency and Disaster Medicine, Hyogo College of Medicine

• NAMBA Mitsuyoshi

  Division of Diabetes and Metabolism, Department of Internal Medicine, Hyogo College of Medicine

抄録

Spontaneously diabetic Torii (SDT) rats were established from Sprague-Dawley (SD) rat and are used as an animal model of type 2 diabetes mellitus. In the present study, the mechanism of the development of injury in the pancreas of these rats was examined focusing on the role of monocytes/macrophages. The number of lymphocytes and monocytes in the circulation of SDT rats increased with age, reaching a plateau at around 9 weeks of age and remaining at that level thereafter. The number of leukocytes in SDT rats was almost twice that of wild-type SD rats. Serum IL-18 levels began to increase at 8 weeks of age, forming a prominent peak at 9 weeks of age. In parallel with this, serum levels of NO₂/NO₃ showed an abrupt rise and decline. Spleen cells prepared from 9-week-old SDT rats expressed high levels of IFN-γ in response to IL-18, while those from 9-week-old wild-type SD rats did not. Immunohistochemical analysis revealed marked infiltration of CD68⁺ cells in the islets of SDT rats. Treatment of SDT rats with Cl₂MDP-liposomes reduced the number of monocytes as well as levels of NO₂/NO₃ in the circulation. Consistent with this, the number of infiltrated CD68⁺ cells in the islets was reduced in SDT rats treated with Cl₂MDP-liposomes. These results suggest that macrophages are involved in pancreatic islet injury in SDT rats through excess production of NO induced by IL-18 which increases transitorily at around 9 weeks of age.<br>

収録刊行物

• Experimental Animals

  Experimental Animals 58 (4), 383-394, 2009

  公益社団法人 日本実験動物学会

キーワード

• Cl₂MDP-liposomes
• IL-18
• monocytes/macrophage
• NO
• SDT rat

詳細情報

• CRID: 1390001205047034112
• NII論文ID: 130000122245
• NII書誌ID: AA11032321
• DOI: 10.1538/expanim.58.383
• COI: 1:CAS:528:DC%2BD1MXhtFChtLvP
• ISSN: 18817122
• ISSN: 00075124
• ISSN: 13411357
• NDL書誌ID: 10283505
• PubMed: 19654436
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10283505
• Web Site: http://www.jstage.jst.go.jp/article/expanim/58/4/58_4_383/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2009345710
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可