The diabetes-prone NZO/Hl strain. II. Pancreatic immunopathology.
Document Type
Article
Publication Date
2002
Keywords
Animals, Diabetes-Mellitus-Type-1, Hyperglycemia, Islets-of-Langerhans, Lymphocyte-Subsets, Male, Mice-Mutant-Strains
First Page
843
Last Page
853
JAX Source
Lab Invest 2002 Jul; 82(7):843-53.
Abstract
We report the first combined light and electron microscopic analysis of the pancreas during the development of type 2 diabetes in the New Zealand Obese (NZO) mouse. As in most other polygenic rodent models of type 2 diabetes, hyperglycemia associated with beta cell destruction is male sex-limited. Increasing degrees of hyperinsulinemia and transition to diabetes were clearly reflected by the islet volume fraction, by the beta cell granulation state, and by ultrastructural changes, primarily of the endoplasmic reticulum. One of the unusual histopathologic features of NZO mice of both sexes was the presence of B-lymphocyte enriched leukocytic aggregates in the pancreas. Immunocytochemical analysis of the pancreas of 52-week-old diabetic males indicated enrichment for CD19(+) B lymphocytes. Staining of adjacent sections for CD3 and CD5 indicated CD5 coexpression on some of the CD19(+) cells, suggesting the presence of the B1-B subset associated with generation of natural autoantibodies in other autoimmune-prone New Zealand mouse strains. In addition, plasma cells in peri-insular leukocytic infiltrates were identified by electron microscopy. Hence, although autoimmunity has previously proven to be a secondary manifestation of beta cell destruction in most rodent models of type 2 diabetes, the present observations suggest that B lymphocyte function, in association with male gender, may contribute to the development of insulin resistance and chronic hyperglycemia in the NZO model.
Recommended Citation
Junger E,
Herberg L,
Jeruschke K,
Leiter EH.
The diabetes-prone NZO/Hl strain. II. Pancreatic immunopathology. Lab Invest 2002 Jul; 82(7):843-53.