DYNAMIC TIME COURSE STUDIES OF THE SPONTANEOUSLY DIABETIC BB WISTAR RAT .3. LIGHT-MICROSCOPIC AND ULTRASTRUCTURAL OBSERVATIONS OF PANCREATIC-ISLETS OF LANGERHANS

Abstract

Pancreatic islet alterations were studied in spontaneously diabetic BB Wistar rats and in young (50 and 65 days old) normoglycemic BB rats with the use of light microscopy, immunohistochemistry and EM. Three groups of diabetic rats were delineated: early diabetes (1-3 days after detection of glycosuria), stable diabetes (41-63 days after detection), and unstable diabetes (7-22 days after detection). In early diabetes, islets were extensively infiltrated by activated lymphocytes and macrophages, and cells demonstrated marked degranulation, injury and necrosis. Although no consistent changes were recorded in A cells, D cells appeared to be decreased in number. In stable and unstable diabetes, islets were small and markedly depleted of B cells, although more insulin-containing cells were identified in the stable group. The number of A and D cells appeared normal in the stable group, although some A cells appeared altered ultrastructurally. In the unstable group both A and D cells appeared decreased, and ultrastructurally altered A cells were again noted. Although B cells appear to be the principal islet target in this model, A and D cells also sustain cellular injury. Variable degrees of insulitis, B cell degranulation and necrosis were documented in 65-day-old normoglycemic BB rats, suggesting that the destruction process in the islets is initiated well in advance of the onset of the clinical syndrome. The pancreases from many diabetic and normoglycemic BB rats also demonstrated mononuclear cell infiltrates distinct from insulitis in periductular and/or acinar locations. These infiltrates, not present in controls, appear to represent an additional morphologic expression of the process responsible for initiating the diabetic state.