ENDOTHELIAL AND MICROVASCULAR ABNORMALITIES IN THE ISLET OF NONOBESE DIABETIC (NOD) MICE - TRANSMISSION AND SCANNING ELECTRON-MICROSCOPIC STUDIES

We studied morphological changes of endothelial cells and the microvascular system in islets of non-obese diabetic (NOD) mice. Transmission electron microscopic examination of islets of 2-3-week-old NOD mice showed that endothelial cells underlain by lymphocytes had irregular apical surface showing an increased number of microvilli and cytoplasmic processes. These morphological changes were observed even in the islets without any apparent beta-cell damage and supposed to be one of the earliest morphological abnormalities in the islet of NOD mice. In 10-15-week-old NOD mice, numerous lymphocytes infiltrate into the islets where high endothelial venules were observed. This finding suggests that abnormalities of capillaries are related to lymphocytic infiltration in type 1 diabetes. Scanning electron microscopic observation of the three-dimensional vascular architectures in the islets of 2-3-week-old NOD mice revealed normal capillary networks as observed in the control mice, whereas the architecture of 10-15-week-old NOD mice showed marked abnormalities: narrowing or occlusion of the capillary lumen and the development of the post-capillary venules. These findings suggest that abnormalities of endothelial cells and microvasculature in the islet play an important role in the pathogenesis and development of type 1 diabetes in the NOD mouse.