Diabetes Manifestation in BB Rats Is Preceded by Pan-pancreatic Presence of Activated Inflammatory Macrophages

Pancreata of normoglycemic diabetes-prone (dp) and diabetes-resistant (dr) BB rats and normal Wistar rats were screened for macrophage infiltration by immunohistochemistry and by electron microscopy. Inflammatory macrophages were found in the endocrine as well as the exocrine part of the pancreata from dp BB rats. In the exocrine tissue they had a different phenotype (ED1+, ED2+, W3/25+, Ox17+) from that found in pancreata from dr BB and Wistar rats (predominantly ED1-, ED2+, W3/25+, Ox17-). The number of macrophages in exocrine portions of pancreata from the various rat strains were not different. By electron microscopy scattered macrophage-associated tissue lesions and phagocytosis of cell debris were found throughout the exocrine tissue and in islets of dp BB rats. Such lesions were low or absent in biopsies of animals that later did not develop diabetes. We conclude that macrophage-mediated cytotoxicity during the early phases of diabetes development in BB rats is not restricted to islets, but is a generalized, pan-pancreatic event.