Insulitis and diabetes are preceded by a decrease in beta cell volume in diabetes-prone BB rats

Immunocytochemistry combined with morphometry was used to test the hypothesis that insulitis and diabetes are preceded by quantitative changes in the pancreas of diabetes-prone BB (DPBB) rats. Diabetes-resistant BB (DRBB) rats of the w-subline served as controls. In the first part of the study rats aged 15, 30, 45, and 60 days were studied. At 60 days preceding both insulitis and onset of diabetes, the DPBB rats demonstrated lower volumes of the entire pancreas, the parenchyma, the endocrine pancreas, and beta, A, and D cells. Body weights of the DPBB rats were lower than the DRBB rats from 15 days of age on. In the second part of the study, DP and DRBB rats were coreared by a foster mother to obtain weight-matched animals. Morphometric analysis at 70 days of age revealed a reduction in both the beta cell volume density and volume whereas no differences were seen in other pancreatic parameters. These results indicate that the appearance of insulitis and the later onset of insulin-dependent diabetes are preceded by a reduction in beta cell volume.