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 affected by genetic background and responds to immunologic and toxic agents, has directed our attention to the need for further study of spontaneous models of diabetes mellitus. This request is for support to study the etiology and 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 diabetic BB/W rats and to define the genetic basis of the syndrome. Support is requested for ultrastructural and immunecytochemical studies of the evolving pancreatic islet and thyroid lesions designed to clarify the pathogenesis of these inflammmatory lesions. The possibility of an immunologic pathogenesis will be explored in islet and thyroid transplantation experiments. Other projects will study the effects of thymus and neonatal bone marrow transplantation, blood transfusions and the transfer of Concanavalin-A stimulated spleen cells between diabetic-prone and resistant animals. Support is also requested for funds to produce BB/N rats for distribution to other established investigators.

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 #
2R37DK019155-12
Application #
3483270
Study Section
Pathology A Study Section (PTHA)
Project Start
1977-09-01
Project End
1991-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
12
Fiscal Year
1986
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
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
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
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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