Diabetes, Vol 42, Issue 4 571-578, Copyright © 1993 by American Diabetes Association

ARTICLES

IDDM in rats induced by thymectomy and irradiation

PA Stumbles and WJ Penhale
Institute for Molecular Genetics and Animal Disease, Murdoch University, Perth, Australia.

A diabetic syndrome closely resembling human IDDM has been induced in rats of specific pathogen-free origin by a combination of thymectomy and irradiation, with an overall incidence (10 wk postirradiation) in female rats of 34% for acute disease and 47% for islet lesions. Males were slightly more susceptible than females. Clinical features of the syndrome included hyperglycemia, insulinopenia, ketosis, and lipidemia, and corresponding islet pathology ranged from diffuse atrophy to focal atrophy and insulitis. Onset was usually acute, and the disease fatal unless early insulin therapy was initiated. Lymphocytic thyroiditis also was observed in a proportion of thymectomized and irradiated rats (49% in females) over the same period but with no apparent correlation to the occurrence of diabetes. A significant decrease in the incidence of disease was found in thymectomized and irradiated rats of conventional origin when compared with genetically identical specific pathogen-free rats, implicating a role for environmental factors in disease susceptibility. Diabetes inducement also was found to be strain related but not RT1u dependent. Both clinical signs and islet lesions were inhibited by early reconstitution of thymectomized and irradiated animals with syngeneic lymphoid cells from normal donors. Islet lesions and glucose intolerance could be transferred to syngeneic recipients by concanavalin A-activated lymphoid cells from acute diabetic donors. The close similarities between this experimental syndrome induced by immunological manipulation and the clinical condition in humans provide further evidence for an immune-mediated pathogenesis for IDDM.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. T. Viehl, T. T. Moore, U. K. Liyanage, D. M. Frey, J. P. Ehlers, T. J. Eberlein, P. S. Goedegebuure, and D. C. Linehan Depletion of CD4+CD25+ Regulatory T Cells Promotes a Tumor-Specific Immune Response in Pancreas Cancer-Bearing Mice Ann. Surg. Oncol., September 1, 2006; 13(9): 1252 - 1258. [Abstract] [Full Text] [PDF]

				J. P. Mordes, D. L. Guberski, J. H. Leif, B. A. Woda, J. F. Flanagan, D. L. Greiner, E. H. Kislauskis, and R. S. Tirabassi LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation Diabetes, September 1, 2005; 54(9): 2727 - 2733. [Abstract] [Full Text] [PDF]

				S. Ramanathan, M.-T. Bihoreau, A. D. Paterson, L. Marandi, D. Gauguier, and P. Poussier Thymectomy and Radiation-Induced Type 1 Diabetes in Nonlymphopenic BB Rats Diabetes, October 1, 2002; 51(10): 2975 - 2981. [Abstract] [Full Text] [PDF]

				U. K. Liyanage, T. T. Moore, H.-G. Joo, Y. Tanaka, V. Herrmann, G. Doherty, J. A. Drebin, S. M. Strasberg, T. J. Eberlein, P. S. Goedegebuure, et al. Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma J. Immunol., September 1, 2002; 169(5): 2756 - 2761. [Abstract] [Full Text] [PDF]

				R. H. Slover and G. S. Eisenbarth Prevention of Type I Diabetes and Recurrent {beta}-Cell Destruction of Transplanted Islets Endocr. Rev., April 1, 1997; 18(2): 241 - 258. [Abstract] [Full Text]

				A. Saoudi, B. Seddon, D. Fowell, and D. Mason The Thymus Contains a High Frequency of Cells that Prevent Autoimmune Diabetes on Transfer into Prediabetic Recipients J. Exp. Med., December 15, 1996; 184(6): 2393 - 2398. [Abstract] [Full Text] [PDF]