Lymphocytic Inflammation of Pancreatic Islets in a Diabetic Cat

Abstract

A preoperative workup prior to minor surgery revealed hyperglycemia (serum glucose = 402 mg/dl; fasting glucose = 271 mg/dl) and marked glucosuria in an 8-year-old spayed female Siamese cat. No clinical signs characteristic of diabetes mellitus (polyuria, polydipsia, polyphagia, weight loss) had been noted. Severe hypoglycemia resulted after a 10fold overdose of NPH insulin (10 units rather than 1) was inadvertently administered to the cat by the owner. Despite medical management, neurologic signs including aggression, seizures, circling, and lack of menace response developed, and the cat died approximately 60 hours after the initial hypoglycemic episode. At necropsy, significant gross lesions were limited to an enlarged fatty liver. Significant histologic lesions involved liver (severe diffuse lipidosis), brain, and pancreas. In the brain, there was central chromatolysis of some hippocampal neurons, a degenerative change for which a specific cause was not definitively determined. In all examined areas of pancreas, most islets (85%; n = 191 islets) were composed partially or entirely of cells with abundant, pale, vacuolated cytoplasm (Fig. 1). Deposition of islet amyloid was not observed, and a Congo red stain for amyloid was negative. Many islets (46%) containing vacuolated cells were mildly to densely infiltrated by small lymphocytes (Fig. 2). Small numbers of lymphocytes were occasionally noted around pancreatic ducts and around some vessels within the interstitium. Pancreatic islet inflammation is unusual in domestic animals, so the lesions were characterized more completely. Deparaffinized 5-μm-thick sections of pancreas were processed for immunohistochemical evaluation. Similar sections of pancreas and lymph node from another adult cat were used as controls. All tissues were fixed by approximately 30 hours of immersion in 10% neutral buffered formalin and then processed routinely for paraffin embedment and sectioning. Polyclonal antibodies used to investigate changes in islet cell populations were against synthetic human glucagon, synthetic human somatostatin, and synthetic human pancreatic polypeptide. A monoclonal anti-human insulin (clone AE9D6) was used to immunolabel pancreatic islet s cells. Polyclonal and monoclonalc, anti-human CD3 antibodies and a monoclonal anti-human CD5 were used as T-lymphocyte markers. Monoclonal antibodies to BLA.36 (clone A27-42), B-29, and MB-1 were used as B-lymphocyte markers. Biotin-streptavidin alkaline phosphatase was used for detection of tissue-bound primary antibody. In the control pancreas, the pattern of islet cell immunostaining for the different hormones was similar to that de-