INDUCTION OF DIABETES IN PVG/C STRAIN RATS BY MANIPULATION OF THE IMMUNE-SYSTEM

被引:22
作者
PENHALE, WJ
STUMBLES, PA
HUXTABLE, CR
SUTHERLAND, RJ
PETHICK, DW
机构
[1] Divisions of Veterinary Biology and Applied, Veterinary Medicine, Murdoch University, Murdoch, WA
关键词
Autoimmunity; Insulitis; Irradiation; Islet atrophy; Thymectomy; Type 1 (insulin-dependent) diabetes;
D O I
10.3109/08916939008993389
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A combination of thymectomy and sublethal irradiation (Tx-X) consistently induced diabetes in female rats of the PVG/c strain. The incidence of diabetes varied from 10.7% to 53.4% in seven successive Tx-X groups (mean 29.7% Both clinical and subclinical disease was observed with the majority of affected animals developing the former condition. This was acute in onset, rapidly fatal (1-4 days) and characterised by ketosis and lipidaemia. Overtly diabetic rats had markedly raised plasma glucose concentrations compared to normal rats of the same strain and plasma immunoreactive insulin concentrations were comspondingly depressed in this group. Histopathological change within the islets of Langehans correlated with clinical status and ranged from diffuse atrophy in the majority of the acutely diabetic rats to mild and focal lymphocytic insulitis in a proportion of the non-diabetic rats. Islet cell autoantibodies were demonstrated by indirect immunofluorescence in approximately 25% of clinically diabetic animals. The majority of diabetic rats were found to be responsive to insulin and the clinical signs could be reversed by daily parented insulin administration. These observations implicate the immune system in diabetes generation and are consistent with an immune mediated pathogenesis as the underlying cause of the islet cell destruction. This syndrome may thus be a potentially useful animal model for type 1 (insulin dependent) diabetes in man. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
引用
收藏
页码:169 / 179
页数:11
相关论文
共 11 条
[1]  
Like A.A., Appel M.C., Rossini A.A., Autoantibodies in the BB/W rat, Diabetes, 31, pp. 816-820, (1982)
[2]  
Ndmp J., Lemmark M.D.M., Autoimmunity in insulin-dependent diabetes, Am. J. Med, 70, pp. 135-140, (1981)
[3]  
Boitard C., McDevitt H.O., Immunology of insulin-dependent diabetes mellitus, Perspectives on Autoimmunity, pp. 34-58, (1988)
[4]  
Penhale W.J., Farmer A., McKenna R.P., Irvine W.J., Spontaneous thyroiditis in thymectomized and irradiated Wistar rats, Clin. exp. Immunol, 15, pp. 225-236, (1973)
[5]  
Penhale W.J., Irvine W.J., Inglis J.M.R., Farmer A., Thyroiditis in T cell depleted rats: Suppression of the autoallergic response by reconstitution with normal lymphoid cells, Clin. exp. Immunol, 25, pp. 6-16, (1976)
[6]  
Ansar Ahmed S., Penhale W.J., Thyroid transplantation in rats developing autoimmune thyroiditis following thymectomy and irradiation, Clin. exp. Immunol, 45, pp. 480-486, (1981)
[7]  
Seemayer T.A., Tannenbaum G.S., Goldman H., Colle E., Animal model: Spontaneous diabetes mellitus in the BB Wistar rat, Am. J. Pathol, 101, pp. 485-488, (1980)
[8]  
Nishiyama R.H., Torreui D.B., Martin S., Pek Belbez S., Keren D.F., The detection of islet-cell antibodies by immunofluorescence on Bouin's-fmed paraffim-embedded human pancreas, Lab. Invest, 43, 2, pp. 191-195, (1980)
[9]  
Williamson D.H., Mellanby J., Krebs H.A., Enzymic determination of D-3-hydroxybutync acid and aceto acetic acid in blood, Eiochem. J, 82, pp. 90-96, (1962)
[10]  
McGregor A.M., Rennie D.P., Weetman A.P., Massman R.A., Foord S.M., Dieguez C., Hall R., The influence of cyclosporin A on experimental autoimmune thyroid disease in the rat, Life Sciences, 32, pp. 97-108, (1983)