Histopathological and Immunohistochemical Analysis of the Endocrine and Exocrine Pancreas in Twelve Cattle with Insulin-Dependent Diabetes Mellitus (IDDM)

Abstract

Histological and immunohistochemical studies were carried out on the pancreas of twelve cattle of insulin-dependent diabetes mellitus (IDDM). They showed clinical signs such as persistent hyperglycemia, glycosuria and decreased glucose tolerance, and some cases accompanied with or without ketonuria. Histopathologically, eight cattle were diagnosed as chronic IDDM, while others were acute IDDM. The most characteristic lesions of the pancreas in chronic IDDM showed a decrease in the size and number of pancreatic islets, interlobular and interacinar fibrosis, mild lymphocytic insulitis, and vacuolation of a few islets. Almost all cells in the atrophied islets had a small amount of ungranulated cytoplasm. Immunohistochemical examination revealed that the atrophied islet cells did not react to anti-insulin antibody, but occasionally reacted to anti-glucagon or somatostatin antibodies. A few solitary islets with mild lymphocytic infiltration, necrotic islets with occasional calcification, and atrophied islets with mild fibrosis were also observed. A few islets consisted of many islet cells with vacuolated cytoplasm including a small number of insulin-positive granules. Accumulation of glycogen granules was occasionally observed in these islets. Islet fibrosis was due to the proliferation of collagen fibers reactive to both anti-collagen type I and type III antibodies. In acute IDDM, the major islets consisted of the cells with vacuolated cytoplasm indicating the degranulation of islet cells. These islets contained many islet cells with shrunken cytoplasm and karyorrhectic nuclei. Lymphocytic infiltration was frequently observed in the islets which consisted of many islet cells having karyorrhectic nuclei and vacuolated and severely degranulated cytoplasm. Immunohistochemically, islet cells with vacuolated cytoplasm had a small amount of insulin-positive granules, suggesting severe degranulation of beta-cells. An increase in acinar islet-cells and proliferation of ductal epithelial cells showing insulin-immunoreactivity were observed. Bovine IgG-immunoreactive islet cells were frequently seen in the vacuolated islets. In summary, pathological observations suggested that beta-cells were being destroyed by an inflammatory process which selectively affected the pancreatic islets. Lymphocytic insulitis and anti-bovine immunoreactive islet cells were thought to be the most significant changes in determining the etiology and pathogenesis of bovine IDDM, and suggested their role in anti-islet autoimmunity in this form of diabetes.

Serum amylase activity disorders in the course of experimental diabetes in rabbits

“…Clinical investigations and experimental laboratory research supported by morphological and ultrastructural observations indicate a close relation between pancreatic exo-and endocrine parts (Okabayashi et al, 1988;Aughsteen and Kataoka, 1993;Meral et al, 2001) Insulin and glucagon actions have been investigated in great detail and clinical studies in diabetic patients show that the impairment of pancreatic exocrine functions is due to insulin deficiency and relative glucagon predominance (Adeghate, 1999;Taniyama et al, 1999;Hardt et al, 2000;Lernmark, 2000;Harding et al, 2001). Reports regarding the influence of insulin deficiency on the pancreatic exocrine function describe distinctive changes in composition and quality of pancreatic juice as well as its decreased production (Okabayashi et al, 1988;Aughsteen and Kataoka, 1993;Kim et al, 2000).…”

“…Interestingly, the relation between insulin and glucagon concentrations in extracellular fluid and their antagonistic actions also seem to play a key role in pancreatic exocrine function disorders. Insulin is recognised as the main factor stimulating exocrine activity, whilst glucagon is ascribed an inhibitory role, not only in the processes of synthesis but also in the secretion of amylase and HCO 3 -ions (Taniyama et al, 1999;Hardt et al, 2000), as shown in both functional tests as decreased enzyme activity and ionic shi�s, and in histopathological observations in the form of involutional changes, exocrine cell degranulation and texture atrophy (Minami et al, 1999;Harding et al, 2001). Amylase -one of the main enzymes produced in exocrine pancreatic cells, may be recognised as an adequate indicator of organ's activity both in physiological and pathological states.…”

Improvement of insulin response in the streptozotocin model of insulin-dependent diabetes mellitus. Insulin response with and without a long-acting insulin treatment

“…The major type of diabetes mellitus observed in dogs and cats is insulin-dependent at the time of diagnosis (Feldman and Nelson, 2004;Rand and Marshall, 2005), and in cattle, insulinopenic diabetes is known to develop after infection with bovine viral diarrhea virus (Taniyama et al, 1999). Thus, the fact cannot be excluded that these results could also be beneficial in clinical veterinary settings.…”

Spontaneous Diabetes Mellitus in Animals

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[23][24][25][26]. Young individuals are constantly affected, the age ranging between 6 months and 5 years of age.

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“…The results of these tests proved that the glucose disappearance rate and half time were longer than in normal control cows. Elevated values of serum fructosamine were also observed [22,25]. …”