N-acetyl-cysteine accelerates transfer of diabetes into non-obese diabetic scid mice

J. Irie, A. Shimada, Y. Oikawa, T. Shigihara, T. Saruta

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims/hypothesis. Type 1 diabetes mellitus is caused by autoimmune pancreatic beta cell destruction, and the destructive process involves several molecular mechanisms including oxygen-reactive species. A cysteine derivative, N-acetyl-cysteine, is widely used as an antioxidant, but the role of N-acetyl-cysteine in the protection of pancreatic beta cells in Type 1 diabetes remains unclear. The aim of this study was to clarify the effect of N-acetyl-cysteine on beta cells using an adoptive transfer system in a murine model of Type 1 diabetes. Methods. Splenocytes from diabetic female non-obese diabetic mice were transferred into female non-obese diabetic scid/scid recipients to induce diabetes. Just after transfer, N-acetyl-cysteine was administered to non-obese diabetic scid recipients. Two weeks after transfer, the pancreas of the recipients was examined histologically, and cytokine mRNA expression in the pancreas was analysed. In vitro, CD4-positive splenocytes from diabetic donor mice were stimulated with anti-CD3 and anti-CD28 antibodies with or without N-acetyl-cysteine. Results. Treatment with N-acetyl-cysteine significantly accelerated the transfer of diabetes into non-obese diabetic scid recipients. Treatment with N-acetyl-cysteine accelerated the infiltration of mononuclear cells accompanied by CD8-positive cells into the intra-islet region of the recipient's pancreas, and enhanced interferon-gamma mRNA expression in the pancreas. In vitro, treatment with N-acetyl-cysteine enhanced interferon-gamma and interleukin-2 production by CD4-positive splenocytes of the diabetic donor mice. Conclusions/interpretation. N-acetyl-cysteine accelerates the transfer of diabetes into non-obese diabetic scid mice and this effect is accompanied by the promotion of local infiltration and T-helper cell type 1 responses.

Original languageEnglish
Pages (from-to)1803-1809
Number of pages7
JournalDiabetologia
Volume47
Issue number10
DOIs
Publication statusPublished - 2004 Oct 1

Keywords

  • Antioxidant
  • Non-obese diabetic mouse
  • T-helper cell type 1/2

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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