Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM019155-11
Application #
3151193
Study Section
(SSS)
Project Start
1977-09-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code

  Publications

Cohen, A J; McGill, P D; Rossetti, R G et al. (1987) Glomerulopathy in spontaneously diabetic rat. Impact of glycemic control. Diabetes 36:944-51
Mordes, J P; Handler, E S; Like, A A et al. (1986) Irradiated lymphocytes do not adoptively transfer diabetes or prevent spontaneous disease in the BB/W rat. Metabolism 35:552-4
Woda, B A; Like, A A; Padden, C et al. (1986) Deficiency of phenotypic cytotoxic-suppressor T lymphocytes in the BB/W rat. J Immunol 136:856-9
Like, A A; Guberski, D L; Butler, L (1986) Diabetic BioBreeding/Worcester (BB/Wor) rats need not be lymphopenic. J Immunol 136:3254-8
Weringer, E J; Like, A A (1986) Diabetes mellitus in the BB/W rat. Insulitis in pancreatic islet grafts after transplantation in diabetic recipients. Am J Pathol 125:107-12
Like, A A; Biron, C A; Weringer, E J et al. (1986) Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. J Exp Med 164:1145-59
Weringer, E J; Like, A A (1985) Immune attack on pancreatic islet transplants in the spontaneously diabetic BioBreeding/Worcester (BB/W) rat is not MHC restricted. J Immunol 134:2383-6
Like, A A; Weringer, E J; Holdash, A et al. (1985) Adoptive transfer of autoimmune diabetes mellitus in biobreeding/Worcester (BB/W) inbred and hybrid rats. J Immunol 134:1583-7
Rossini, A A; Mordes, J P; Like, A A (1985) Immunology of insulin-dependent diabetes mellitus. Annu Rev Immunol 3:289-320
Gallina, D L; Pelletier, D; Doherty, P et al. (1985) 111Indium-labelled lymphocytes do not image or label the pancreas of the BB/W rat. Diabetologia 28:143-7

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