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Toxicol Appl Pharmacol. 2015 Apr 15;284(2):254-61. doi: 10.1016/j.taap.2014.12.016. Epub 2015 Jan 7.

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

Author information

1
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea.
2
Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827, Republic of Korea.
3
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea; Endocrinology, Internal Medicine, Gachon University Gil Medical Center, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760, Republic of Korea; Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760, Republic of Korea.
4
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea; College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea; Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760, Republic of Korea. Electronic address: hsjun@gachon.ac.kr.

Abstract

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 (5mg/kg/day) from 8weeks of age for 8weeks. The cumulative incidence of diabetes was monitored until 30weeks 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 T 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.

KEYWORDS:

Autoimmune; Glut1; Non-obese diabetic mice; Proliferation; Sodium meta-arsenite; Type 1 diabetes

PMID:
25576766
DOI:
10.1016/j.taap.2014.12.016
[Indexed for MEDLINE]

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