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Title: Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory Tmore » cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose transporter 1 (Glut1) in splenocytes.« less
Authors:
; ;  [1] ;  [2] ;  [1] ;  [3] ;  [3] ;  [1] ;  [3] ;  [3]
  1. Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of)
  2. Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827 (Korea, Republic of)
  3. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22465742
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 284; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARSENIC COMPOUNDS; CELL PROLIFERATION; DISEASES; FEMALES; GLUCOSE; HISTOLOGY; IN VITRO; IN VIVO; LYMPHOCYTES; MICE; MONITORS; SODIUM; SPLEEN; TRANSPORT