The hypothesis that the pancreatic beta cell is a primary site of pathology in human and experimental diabetes, and the knowledge that the beta cell population is affected by genetic background and responds to immunologic injury has directed our attention to the need for further study of spontaneous models of diabetes mellitus. This request is for support of research projects designed to study the pathogenesis of diabetes in a unique model of insulin- dependent diabetes, the Bio Breeding/Worcester (BB/W) rat. Support is requested for breeding and related experiments designed to establish inbred lines of diabetes-prone and diabetes- resistant BB/W rats and to define the genetic basis of the syndrome. Support is requested for studies of the cellular mechanism of beta cell destruction and of the resistance to beta injury. Islet transplantation and adoptive transfer experiments will explore the role of MHC restriction in the destruction of pancreatic beta cells. Virtually all of the proposed experiments are immunopathologic in nature. As such, all incorporate essential morphologic read out systems including routine light microscopy, immunohistochemistry and electron microscopy of tissues as well as flow cytometry techniques for the identification of lymphocyte subsets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37DK019155-17
Application #
3483271
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-09-01
Project End
1994-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Ellerman, K E; Like, A A (2000) Susceptibility to diabetes is widely distributed in normal class IIu haplotype rats. Diabetologia 43:890-8
Ellerman, K E; Like, A A (1999) Islet cell membrane antigens activate diabetogenic CD4+ T-cells in the BB/Wor rat. Diabetes 48:975-82
Ellerman, K E; Richards, C A; Guberski, D L et al. (1996) Kilham rat triggers T-cell-dependent autoimmune diabetes in multiple strains of rat. Diabetes 45:557-62
Ellerman, K E; Like, A A (1995) A major histocompatibility complex class II restriction for BioBreeding/Worcester diabetes-inducing T cells. J Exp Med 182:923-30
Stubbs, M; Guberski, D L; Like, A A (1994) Preservation of GLUT 2 expression in islet beta cells of Kilham rat virus (KRV)-infected diabetes-resistant BB/Wor rats. Diabetologia 37:1186-94
Guberski, D L; Butler, L; Manzi, S M et al. (1993) The BBZ/Wor rat: clinical characteristics of the diabetic syndrome. Diabetologia 36:912-9
Ellerman, K; Wrobleski, M; Rabinovitch, A et al. (1993) Natural killer cell depletion and diabetes mellitus in the BB/Wor rat (revisited). Diabetologia 36:596-601
Brown, D W; Welsh, R M; Like, A A (1993) Infection of peripancreatic lymph nodes but not islets precedes Kilham rat virus-induced diabetes in BB/Wor rats. J Virol 67:5873-8
Barlow, A K; Like, A A (1992) Anti-CD2 monoclonal antibodies prevent spontaneous and adoptive transfer of diabetes in the BB/Wor rat. Am J Pathol 141:1043-51
Like, A A; Guberski, D L; Butler, L (1991) Influence of environmental viral agents on frequency and tempo of diabetes mellitus in BB/Wor rats. Diabetes 40:259-62

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