SDTラットの膵島障害進展におけるマクロファージの役割 Role of Macrophages in the Development of Pancreatic Islet Injury in Spontaneously Diabetic Torii Rats

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Author(s)

    • 井野口 千枝 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
    • 上田 晴康 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
    • MIYAGAWA Jun-ichiro
    • Division of Diabetes and Metabolism, Department of Internal Medicine, Hyogo College of Medicine
    • 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

Abstract

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 NO<sub>2</sub>/NO<sub>3</sub> 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<sup>+</sup> cells in the islets of SDT rats. Treatment of SDT rats with Cl<sub>2</sub>MDP-liposomes reduced the number of monocytes as well as levels of NO<sub>2</sub>/NO<sub>3</sub> in the circulation. Consistent with this, the number of infiltrated CD68<sup>+</sup> cells in the islets was reduced in SDT rats treated with Cl<sub>2</sub>MDP-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>

Journal

  • Experimental Animals

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

    Japanese Association for Laboratory Animal Science

Codes

  • NII Article ID (NAID)
    130000122245
  • NII NACSIS-CAT ID (NCID)
    AA11032321
  • Text Lang
    ENG
  • ISSN
    1341-1357
  • NDL Article ID
    10283505
  • NDL Source Classification
    ZS7(科学技術--医学)
  • NDL Call No.
    Z54-H752
  • Data Source
    NDL  J-STAGE 
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