title: Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice.
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.
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea.
authors.forename: D
authors.initials: D
authors.lastname: Kim
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea.
authors.forename: E K
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: C S
authors.initials: CS
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: H S
authors.initials: HS
authors.lastname: Jun
mesh_terms: D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000378:metabolism / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010766:Phosphorylation / Q000187:drug effects; D017670:Sodium Compounds / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
chemical_list: D018053:Arsenites; D051272:Glucose Transporter Type 1; C495678:Slc2a1 protein, mouse; D017670:Sodium Compounds; D015847:Interleukin-4; C017947:sodium arsenite; D007371:Interferon-gamma
keywords: Autoimmune; Glut1; Non-obese diabetic mice; Proliferation; Sodium meta-arsenite; Type 1 diabetes