Histopathological and immunohistochemical analysis of the endocrine and exocrine pancreas in twelve cattle with insulin-dependent diabetes mellitus (IDDM)

Histological and immunohistochemical studies were carried out on the pancre as of twelve cattle of insulin-dependent diabetes mellitus (IDDM). They sho wed clinical signs such as persistent hyperglycemia, glycosuria and decreas ed glucose tolerance, and some cases accompanied with or without ketonuria. Histopathologically, eight cattle were diagnosed as chronic IDDM, while ot hers were acute IDDM. The most characteristic lesions of the pancreas in ch ronic IDDM showed a decrease in the size and number of pancreatic islets, i nterlobular and interacinar fibrosis, mild lymphocytic insulitis, and vacuo lation of a few islets. Almost all cells in the atrophied islets had a smal l amount of ungranulated cytoplasm. Immunohistochemical examination reveale d that the atrophied islet cells did not react to antiinsulin antibody, but occasionally reacted to anti-glucagon or somatostatin antibodies. A few so litary islets with mild lymphocytic infiltration, necrotic islets with occa sional calcification, and atrophied islets with mild fibrosis were also obs erved. A few islets consisted of many islet cells with vacuolated cytoplasm including a small number of insulin-positive granules. Accumulation of gly cogen granules was occasionally observed in these islets. Islet fibrosis wa s due to the proliferation of collagen fibers reactive to both anti-collage n type I and type III antibodies. In acute IDDM, the major islets consisted of the cells with vacuolated cytoplasm indicating the degranulation of isl et cells. These islets contained many islet cells with shrunken cytoplasm a nd karyorrhectic nuclei. Lymphocytic infiltration was frequently observed i n the islets which consisted of many islet cells having karyorrhectic nucle i and vacuolated and severely degranulated cytoplasm. Immunohistochemically , islet cells with vacuolated cytoplasm had a small amount of insulin-posit ive granules, suggesting severe degranulation of beta-cells. An increase in acinar islet-cells and proliferation of ductal epithelial cells showing in sulin-immunoreactivity were observed. Bovine IgG-immunoreactive islet cells were frequently seen in the vacuolated islets. In summary, pathological ob servations suggested that beta-cells were being destroyed by an inflammator y process which selectively affected the pancreatic islets. Lymphocytic ins ulitis and anti-bovine immunoreactive islet, cells were thought to be the m ost significant changes in determining the etiology and pathogenesis of bov ine IDDM, and suggested their role in anti- islet autoimmunity in this form of diabetes.