Immunohistochemical detection of the enzyme glutamic acid decarboxylase and hormones of the islets of Langerhans in spontaneous insulin-dependent diabetes mellitus in cattle

Immunohistochemical expression of glutamic acid decarboxylase (GAD) enzyme was detected in the pancreatic islets of 12 cattle with spontaneous insulin-dependent diabetes mellitus (IDDM). The most characteristic changes were atrophy and decreased number of pancreatic islets, enlarged islets with vacuolated beta cells, and lymphocytic islet adenitis. Atrophied islets were composed of small islet cells without cytoplasmic insulin-positive granules. Immunohistochemically, GAD was not found in the cytoplasm of atrophied islet cells. Furthermore, enlarged islets consisting of islet cells with vacuolated cytoplasm were frequently observed. The cytoplasm of vacuolated cells contained very few GAD- and insulin-positive granules, indicating beta cell destruction. Enlarged islets with mild lymphocytic infiltrates were frequently observed. These findings suggest that islet cells in cattle with IDDM lose their insulin synthesis function and their ability to regulate hormonal secretion of alpha and delta cells.     

Immunohistochemical studies on the splenic lobe of the pancreas in young Japanese quails (Coturnix c. japonica)

The splenic lobe (Lobus splenicus) of the pancreas of young meat-type quails (Coturnix c. japonica) was examined by immunohistochemical and light microscopic methods. The endocrine cells are mainly grouped as alpha, beta and mixed islets. A large region consisting of alpha cells is located in the central region of the splenic lobe whereas numerous beta islets are detected in the periphery of the splenic lobe. Alpha islets are in the majority composed of toluidine blue positive A cells and a few toluidine blue negative D and / or avian pancreatic polypeptide (APP) endocrine cells. Beta islets contain only a few toluidine blue negative B and a few D cells. Immunohistochemical staining of the splenic lobe reveal in the centre of beta islets numerous insulin immunoreactive cells and scarcely in alpha islets, exocrine tissue and / or among acinar cells. Somatostatin immune-reactive cells form a circular layer in the periphery of beta islets whereas these cells are uniformly distributed throughout the alpha islet parenchyma and exocrine tissue. In conclusion, the morphology but also the endo- and exocrine functions of the splenic lobe of quails are similar to observations in other avian species such as chicken, duck, goose and pigeon.     

Diabetes mellitus in a domesticated Spanish mustang

An 18-year-old Spanish Mustang mare was referred for evaluation of progressive weight loss and persistent hyperglycemia. Clinicopathologic abnormalities included marked hyperglycemia and glycosuria. Serum cortisol concentration was appropriately decreased following administration of dexamethasone, indicating that the horse did not have pituitary pars intermedia dysfunction. Serum insulin and plasma C-peptide concentrations were low, suggesting that hyperglycemia was a result of decreased secretion of insulin by pancreatic beta cells. In addition, glucose concentration did not return to the baseline concentration until 5 hours after i.v. administration of a glucose bolus, suggesting that insulin secretion, insulin effect, or both were reduced. However, i.v. administration of insulin caused only a slight decrease in the plasma glucose concentration, giving the impression that the action of insulin was impaired. Within 5 hours after administration of a combination of glyburide and metformin, which is used to treat diabetes mellitus in humans, the glucose concentration was within reference limits. The horse was euthanized, and a postmortem examination was done. Immunohistochemical staining of sections of the pancreas revealed attenuation of the pancreatic islet beta-cell population, with beta cells that remained generally limited to the periphery of the islets. These findings indicate that, albeit rare, pancreatic beta-cell failure may contribute to the development of diabetes mellitus in horses.     

Microanatomic features of pancreatic islets and immunolocalization of glucose transporters in tissues of llamas and alpacas

OBJECTIVE: To describe the microanatomic features of pancreatic islets and the immunohistochemical distribution of glucose transporter (GLUT) molecules in the pancreas and other tissues of New World camelids. ANIMALS: 7 healthy adult New World camelids, 2 neonatal camelids with developmental skeletal abnormalities, and 2 BALB/c mice. PROCEDURE: Samples of pancreas, liver, skeletal muscle, mammary gland, brain, and adipose tissue were collected postmortem from camelids and mice. Pancreatic tissue sections from camelids were assessed microscopically. Sections of all tissues from camelids and mice (positive control specimens) were examined after staining with antibodies against GLUT-1, -2, -3, and -4 molecules. RESULTS: In camelids, pancreatic islets were prominent and lacked connective tissue capsules. Numerous individual endocrine-type cells were visible distant from the islets. Findings in neonatal and adult tissues were similar; however, the former appeared to have more non-islet-associated endocrine cells. Via immunostaining, GLUT-2 molecules were detected on pancreatic endocrine cells and hepatocytes in camelids, GLUT-1 molecules were detected on the capillary endothelium of the CNS, GLUT-3 molecules were detected throughout the gray matter, and GLUT-4 molecules were not detected in any camelid tissues. Staining characteristics of neonatal and adult tissues were similar. CONCLUSIONS AND CLINICAL RELEVANCE: In New World camelids, microanatomic features of pancreatic islets are similar to those of other mammals. Data suggest that the poor glucose clearance and poor insulin response to hyperglycemia in adult camelids cannot be attributed to a lack of islet cells or lack of GLUT molecules on the outer membrane of those cells.     

The production of a diabetic mouse using constructs encoding porcine insulin promoter-driven mutant human hepatocyte nuclear factor-1alpha

A diabetic mouse model was produced using a mutant human hepatocyte nuclear factor-1alpha gene (HNF1alphaP291fsinsC) regulated by the porcine insulin promoter. The functionality of two different constructs containing HNF1alphaP291fsinsC, termed PD1 and PD2 (cytomegalovirus enhancer minus and plus), were examined in transgenic mice. The blood glucose levels and body weights of the PD1 transgenic mice did not differ from their non-transgenic littermates over the period from 3 to 8 weeks of age. Conversely, the PD2 transgenic mice exhibited hyperglycemia and decreased body weight. Western blot analysis demonstrated that mutant HNF-1alpha protein (HNF1alphaP291), derived from the PD2 transgene, was expressed in the PD2 mice. Morphometric studies of the pancreas of a PD2 mouse revealed that the number of pancreatic islets present was less than that in the non-transgenic mice, indicating disturbed islet neogenesis. These results suggest that impaired insulin secretion in disrupted islets causes hyperglycemia. In addition, the phenotype of PD2 transgenic mice similar to that of the HNF-1alpha gene-deficient mouse, which displays growth retardation and impaired viability. These results indicate that HNF1alphaP291 expression driven by the porcine insulin promoter, together with the cytomegalovirus enhancer, induces a diabetic phenotype in transgenic mice.     

Immunocytochemistry of normal pancreatic islets and spontaneous islet cell tumors in dogs

Immunocytochemical studies of the distribution of glucagon, gastrin, insulin, and somatostatin in normal canine pancreatic islets and 20 canine islet cell tumors were done using the peroxidase-anti-peroxidase (PAP) technique. In the normal adult canine pancreas, islets typically consisted of clusters of 20-30 cells, but smaller foci and even individual cells were identified. Alpha cells (glucagon) were often peripherally located, beta cells (insulin) were centrally located and most numerous, and delta cells (somatostatin) were the least numerous and randomly located. Both juvenile and adult canine pancreases did not stain for gastrin. Of the 20 tumors examined, 18 had positive immunoreactivity for insulin, nine for glucagon, 14 for somatostatin, and one for gastrin. Two tumors were uninterpretable due to autolysis. Three tumors were pure insulinomas, but no pure somatostatinomas, glucagonomas, or gastrinomas were identified. Most tumors and metastases had mixed positive immunoreactivity; one neoplastic cell type predominated with lesser numbers of other cell types. Metastatic sites (liver and lymph node) stained for insulin and somatostatin, only. Foci of non-neoplastic islet cell tissue (nesidioblastosis), often located at the pancreatic-mesenteric junction, stained strongly positive for insulin, glucagon, and somatostatin but not for gastrin. The tumor staining pattern did not consistently correlate with tumor function, as determined by blood glucose and serum insulin assays. The PAP technique works well on paraffin-embedded, formalin-fixed tissue using rabbit or guinea pig antisera as the primary antibody. Staining occurred on sections of paraffin blocks stored for up to 7 years.     

Localization of amylin‐like immunoreactivity in the striped velvet gecko pancreas

Immunohistochemical techniques were employed to investigate the distribution of amylin‐like immunoreactive cells in the pancreas of gecko Homopholis fasciata. Four types of endocrine cells were distinguished: insulin immunoreactive (B cells), pancreatic polypeptide immunoreactive (PP cells), glucagon and pancreatic polypeptide immunoreactive (A/PP cells) and somatostatin immunoreactive cells (D cells). Pancreatic islets contained B, A/PP and D cells, whereas extrainsular regions contained B, D and PP cells. In the pancreatic islets, amylin‐like immunoreactive cells corresponded to B cells, but not to A/PP or D cells. In the extrainsular regions, amylin‐like immunoreactive cells corresponded to either B or PP cells. Amylin secreted from intrainsular B cells may regulate pancreatic hormone secretion in an autocrine and/or a paracrine fashion. On the other hand, amylin secreted from extrainsular PP and B cells, and/or intrainsular B cells may participate in the modulation of calcium homoeostasis in an endocrine fashion.     

Immunohistochemical morphometry of pancreatic islets in the cat.

The application of immunohistochemical technique with antisera for glucagon (Glu), insulin (Ins), somatostatin (Som) and pancreatic polypeptide (PP) to serial sections of the cat pancreas permitted the quantitative evaluation of the population of 4 endocrine cell types and that of the area, larger diameter and density of islets. The pancreas was divided macroscopically into the 4 portions, duodenal, gastric, anastomotic and splenic. The duodenal portion was characterized by the localization of PP-immunoreactive (IR) cell-rich islets, the dissemination of PP-IR cells in the exocrine parenchyma and the absence of Glu-IR cells. In the duodenal portion, the area, the larger diameter and the density of islets were significantly smaller than those in the other 3 portions. On the contrary, the other 3 portions were marked with the deficiency of PP-IR cells and the existence of Glu-IR cell-rich islets. Ins-IR cells, identified as compact cell masses without any other types of cells, occupied a major part of every islet, composing much the same population throughout the 4 portions. The Som-IR cell population appeared to be closely in parallel with the Glu-IR cell population in all of the portions. It is concluded that all islets are similar in the Ins-IR cell population, but different in the complementary arrangement of Glu- and PP-IR cells. Based on this difference, 2 types of islets can be classified.     

Ultrastructure of pancreatic alpha and beta cells in young quails (Coturnix coturnix japonica) fed aflatoxin

The present investigation was undertaken to assess the effects of aflatoxin (AF) containing diets on alpha and beta cells of the endocrine pancreas in young quails by means of light and electron microscopy. A total of thirty quails were divided into 3 groups, each comprising 10 animals. Total AF was incorporated into the diet of these groups, at dosages of 0 (control, group 1), 2.5 (group 2), and 5.0 (group 3) mg AF/kg feed. The chicks were housed in electrically heated battery cages and exposed to light for 24 h from hatching to 3 weeks of age. Quails consumed the diets and water ad libitum. Electron microscopic examinations demonstrated degranulation of alpha cells, decrease in the size and number of secreting granules, and increase in the number of free ribosomes and polisomes in the animals of group 2 and 3. In beta cells, the numbers of free ribosomes and polisomes decreased, whereas the number of mature granules increased in the animals of group 3. Mononuclear cell infiltrates were observed in the periphery of capillaries and around endocrine islets in the experimental groups. Furthermore, capillaries of the animals in group 2 and 3 were dilated at all sides of both alpha and beta islets. According to the results of this study, the addition of aflatoxin to the diets of quails at dosage of 2.5 and 5 mg AF/kg leads to significant changes in pancreatic alpha and beta cells. These changes may exhibit adverse effect on the metabolism of carbohydrates in poultry.     

An investigation of the relationship between duct system and A cell-rich and PP cell-rich pancreatic islets in the canine pancreas.

The pancreata of four six-month-old dogs of the same mother, two with both the pancreatic and accessory pancreatic ducts (X-type) and two with only the accessory pancreatic duct (Y-type), were examined in this study. To clarify the relationships between the type of pancreatic duct system and the composition of pancreatic endocrine cells, the pancreata were examined immunohistochemically using antiserum against four types of pancreatic hormones (glucagon, insulin, somatostatin and pancreatic polypeptide). In all areas of the X- and Y-type duct system pancreata, B cells accounted for 52-82% of the total number of islet cells, and D cells accounted for 4-15%. In the X-type ducts system, the percentages of A and PP cells in the right and left lobes of the pancreas differed greatly. It was found that A and PP cells appear in inverse proportion to each other and that there exist A cell-rich and PP cell-rich pancreatic islets. The A cell-rich pancreatic islets appeared in the left lobes along the accessory pancreatic duct, while the PP cell-rich pancreatic islets were observed in the right lobes along the pancreatic duct. The body of the pancreas contained both A cell-rich and PP cell-rich pancreatic islets. In the Y-type duct systems, A cell-rich pancreatic islets appeared in the right lobes. These findings indicate that the composition of A and PP cells in pancreatic islets is closely related to the type of duct system.     

Impaired pancreatic endocrine and exocrine responses in growth-retarded piglets

The alteration of pancreatic endocrine and exocrine secretory responses induced by secretagogues and neural input was investigated in post-weaning growth-retarded (GR) piglets. Blood and pancreatic juice were collected from these animals (6-8-weeks old). Plasma insulin and pancreatic digestive enzymes induced by nutrients, drugs and vagal stimulation were measured biochemically. The pancreas was inspected by immunohistochemical analysis. In GR piglets, the plasma glucose and insulin concentrations at the resting state were very low, and the secretory response was also markedly reduced, with maximum inhibition of 90% by glucose administration and 83% by arginine administration. The insulin secretion was not increased by 2-deoxy-D-glucose administration in GR piglets. The pancreatic juice secretions induced by vagal stimulation and secretagogues in GR piglets were not different from those induced in the control piglets. However, amylase activity in the pancreatic juice and in the pancreas was significantly decreased in GR piglets, although trypsin and chymotrypsin activities were not different. In the immunohistochemical analysis, the numbers of islets and the staining degree for insulin antibody also declined in the pancreases of GR piglets. These results indicated the reduction of insulin and amylase secretions from the pancreas in GR piglets, suggesting that a dysfunction of pancreatic endocrine and exocrine secretion during growth after weaning may be an important factor in the induction of growth retardation in piglets.     

鸭胰腺内高血糖素—,胰岛素—和生长抑素—免疫反应细胞的形态及分布

用ABC免疫组织化学方法,对1 周龄绍鸭胰腺内的高血糖素(A)、胰岛素(B)和生长抑素(D)免疫反应细胞的形态及分布进行了观察。结果表明,上述3 种细胞在全胰的分布及形态有差异。A 细胞主要成群散在于A 胰岛,少数位于混合型胰岛的边缘。D 细胞主要散在于A 胰岛中,少数位于B胰岛和混合型胰岛的边缘。B细胞主要呈团块状分布于B胰岛,少数位于混合型胰岛的中央。在胰外分泌部有散在的A 和D 细胞,位于腺泡及导管上皮细胞之间或结缔组织中。A 细胞形态各异,以多边形为主,多数细胞伸出形态多样的胞质突起,伸达胰岛或其他细胞间。D细胞的形态与A 细胞相似。B细胞形态均一,呈圆形或卵圆形,未见胞质突起,在外分泌部未见到B细胞。     

Cellular and Molecular Characterization of a Feline Insulinoma

Background: Insulinoma is an autonomous insulin-secreting islet cell neoplasm that is rarely diagnosed in cats. The clinical and pathological aspects of feline insulinoma have been described previously, but the molecular characteristics of these tumors have not been investigated.
Objectives: The study objectives were to characterize peptide hormone production and determine expression of selected genes involved in glucose metabolism and insulin secretion in a feline insulinoma.
Methods: Immunohistochemistry and RT-PCR were used to examine hormone and gene expression, respectively, by insulinoma cells.
Results: Immunohistochemistry examination indicated that the tumor cells expressed insulin, chromogranin A, and somatostatin but not glucagon or pancreatic polypeptide. The tumor expressed several genes characteristic of pancreatic beta cells (β cells) including insulin ( INS ), glucose transporter 2 ( GLUT2 ), and glucokinase ( GCK ). The tumor also expressed hexokinase 1 ( HK1 ), a glycolytic enzyme not normally expressed in β cells. GCK expression was higher in the insulinoma than in normal pancreas from the same cat. The GCK  :  HK1 ratio was >20-fold higher in insulinoma tissue than in normal pancreas.
Conclusions and Clinical Importance: The feline insulinoma produced several peptide hormones and expressed genes consistent with a β-cell phenotype. The pattern of hexokinase gene expression in tumor cells differed from that of normal pancreas. These findings suggest insulinoma cells may have an increased sensitivity to glucose that could contribute to the abnormal insulin secretory response observed at low serum glucose concentrations.     

Cell-specific localization of the cholecystokininA receptor in the porcine pancreas

Cholecystokinin (CCK) produced in the mucosa of the upper small intestine exerts several biological functions. Its secretion in physiological amounts is modulated by the interaction of extracellular regulators and by binding to intracellular receptors of the target cells. The relative affinity of CCK to its receptor has been characterized in various biological and pharmacological studies and it is now well established that CCK has a higher affinity to the CCKA than to the CCKB receptor. Furthermore CCK influences the secretion of pancreatic enzymes in several species but very little is known about the relationship between CCK and the islet hormone-producing cells in the pig pancreas. The localization of this receptor at the cellular level showed conflicting results in animal studies and has not been described in pigs. The aim of the present study was to characterize the precise cellular location of the CCKA receptor in the porcine pancreas. Polyclonal antiserum was raised against the N-terminal epitope of the CCKA receptor molecule and used for localization studies. Using immunohistochemistry on methanol/acetic acid-fixed, paraffin-embedded pancreas, the CCKA receptor could successfully be localized in islet cells. Parallel staining of serial sections with antibodies directed against insulin and glucagon revealed colocalization with glucagon in alpha cells. No immunoreaction was found in the exocrine pancreas. Our results support the concept that in the porcine species the stimulation of the exocrine pancreas is mediated by the CCKB rather than the CCKA receptor, as it is known for the rat species.     

Immunohistochemical, ultrastructural, and hormonal studies on the endocrine pancreas of voles (Microtus arvalis) with monosodium aspartate-induced diabetes.

A single subcutaneous administration of monosodium aspartate (MSA) to 30 neonatal voles, Microtus arvalis Pallas, induced a diabetes mellitus in 50% of the treated animals in early adulthood. The voles (18 males and 12 females) were weaned at 3 weeks of age and fed pellets for Herbivora and cubed hay. Diabetic voles with glycosuria (nine males and six females) were classified into two groups according to the duration and grade of glycosuria. One group had slight diabetes with glycosuria (+: 0.1%) for 1 week and the other severe diabetes with marked glycosuria ( : greater than or equal to 0.5%) for over 4 weeks. Pancreatic islets of diabetic voles (n = 7) were examined immunohistochemically, light microscopically, and electron microscopically. Blood glucose concentration and tissue content of insulin, glucagon, and somatostatin were also measured. Slightly diabetic voles (n = 3) had enlarged islets, that, viewed by light microscopy, were characterized by hypertrophy and hyperplasia of beta cells with moderate degranulation. No changes were observed in the peripherally located alpha and delta cells; the voles were moderately hyperglycemic, and they had decreased pancreatic insulin content. Severely diabetic voles (n = 4) that had marked hyperglycemia and almost complete loss of insulin content showed marked vacuolation and degranulation of beta cells. In addition, altered distribution of alpha and delta cells from the periphery of the islets to their interior was noted. Ultrastructural examination revealed features compatible with those of hyperfunction of beta cells in the slightly diabetic voles and marked degeneration of beta cells with glycogen accumulation in the severely diabetic voles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid

Thirty-one primary canine pancreatic endocrine tumors and their metastases were studied histologically and immunohistochemically for the presence of insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, and adrenocorticotrophic hormone (ACTH). Tumors were also evaluated for the presence of amyloid. The cytoarchitectural pattern of 25 of 31 primary tumors was predominantly solid, whereas three tumors were mostly glandular, two were unclassified, and one had a gyriform pattern. Cells with insulin immunoreactivity were found in 30 of 31 tumors and were found in all cases in which there was clinical evidence of inappropriate insulin secretion. Insulin was the only hormone demonstrable in three of the 30 tumors, but cells immunoreactive for other hormones were also present in various combinations in most tumors [i.e., glucagon (13 of 30), somatostatin (17 of 30), PP (25 of 30), and gastrin (2 of 30)]. One tumor contained only cells with glucagon and PP immunoreactivity. Amyloid was found in ten of 31 primary tumors but was not detected in metastases. Cells with insulin immunoreactivity were the only cell type consistently present in tumors containing amyloid. Amyloid deposits did not immunoreact with any of the antisera. Seventeen of 31 dogs had metastasis of the pancreatic endocrine tumor to regional lymph nodes, liver, or both. All metastases available for study (15 of 17) contained cells with insulin immunoreactivity and some contained cells with PP or somatostatin immunoreactivity. No statistically significant (P greater than 0.05) differences in tendency to metastasize were found when pancreatic endocrine tumors were compared by region of origin, cytoarchitectural pattern, presence of amyloid, or by number of hormones contained within the tumor.     

Effects of melatonin on islet neogenesis and beta cell apoptosis in streptozotocin-induced diabetic rats: an immunohistochemical study

This investigation was carried out to explore the antidiabetic, antiapoptotic and neogenetic effects of melatonin (MLT) in streptozotocin-induced diabetic rats. Sixty-four male rats were assigned randomly to one of four groups for periods of 21 and 42 d as follows; i) control, ii) MLT, iii) diabetic (DM), and iv) DM + MLT. Immunohistochemical methods were used -with pancreatic tissue to determine the intensity of insulin, caspase-3 and Bcl-x(L) immune reactivities, and new islet formation. In untreated DM rats, BW loss, increased plasma glucose and MLT concentrations, as well as cytoplasmic degranulation and vacuolization were observed. We also observed a marked increase in the number of apoptotic caspase-3 positive cells and a few insulin- positive cells, but not antiapoptotic Bcl-x(L) positive cells. Observations in the DM + MLT-treated group revealed a high intensity of insulin- and antiapoptotic Bcl-x(L) immune reactivities at 21 and 42 d. Moreover, data indicated that MLT may cause beta cell proliferation and that new small islets originate from cells associated with ductal epithelium and from centroacinar cells by day 21. These data indicate that; i) MLT treatment may stimulate neogenesis in the pancreas of diabetic rats, and ii) MLT's antiapoptotic action may increase beta cell differentiation and caspase-3 inactivation or Bcl-x(L) activation.     

Transient clinical diabetes mellitus in cats: 10 cases (1989-1991)

Medical records of 10 cats with transient clinical diabetes mellitus were reviewed. At the time diabetes was diagnosed, clinical signs included polyuria and polydipsia (10 cats), weight loss (8 cats), polyphagia (3 cats), lethargy (2 cats), and inappetence (1 cat). Mean (+/- SD) fasting blood glucose concentration was 454 +/- 121 mg/dL, mean blood glucose concentration during an 8-hour period (MBG/8 hours) was 378 +/- 72 mg/dL, and glycosuria and trace ketonuria were identified in 10 and 5 cats, respectively. Baseline serum insulin concentration was undetectable (6 cats) or within the reference range (4 cats) and serum insulin concentration did not increase after i.v. glucagon administration in any cat. Insulin-antagonistic drugs were being administered to 5 cats and concurrent disorders were identified in all cats. Management of diabetes included administration of glipizide (6 cats), insulin (3 cats), or both (1 cat), discontinuation of insulin-antagonistic drugs, and treatment of concurrent disorders. Insulin and glipizide treatment was discontinued 4-16 weeks (mean, 7 weeks) after the initial diagnosis of diabetes was confirmed. At the time treatment for diabetes was discontinued, clinical signs had resolved, mean fasting blood glucose concentration was 102 +/- 48 mg/dL, MBG/ 8 hours was 96 +/- 32 mg/dL, glycosuria and ketonuria were not identified in any cat, and concurrent disorders (except mild renal insufficiency in 1 cat) had resolved. Significant (P < .05) increases occurred in postglucagon serum insulin concentrations, insulin peak response, and total insulin secretion, compared with values obtained when clinical diabetes was diagnosed. Histologic abnormalities were identified in pancreatic islets of 5 cats in which pancreatic biopsies were obtained and included decreased number of islets (4 cats), islet amyloidosis (3 cats), and vacuolar degeneration of islet cells (3 cats). Mean beta cell density was significantly (P < .001) decreased in diabetic cats compared with control cats (1.4 +/- 0.7 versus 2.6 +/- 0.5%, respectively). Cells within islets stained positive for insulin, however, the number of insulin-staining cells per islet and the intensity of insulin staining were decreased in 5 and 2 cats, respectively. Clinical diabetes had not recurred in 1 cat after 6 years, in 4 cats lost to follow-up after 1.5, 1.5, 2.0, and 2.5 years, and in 2 cats that died 6 months and 5.5 years after clinical diabetes resolved. Clinical diabetes recurred in 3 cats after 6 months, 14 months, and 3.4 years, respectively. These findings suggest that cats with transient clinical diabetes have pancreatic islet pathology, including decreased beta cell density, and that treatment of diabetes and concurrent disorders results in improved beta cell function, reestablishment of euglycemia, and a transition from a clinical to subclinical diabetic state.     

An Immunohistochemical Survey of Catecholamine-synthesizing Enzyme-immunoreactive Nerves and Endocrine Cells in the Bovine Pancreas

The distribution of catecholamine-synthesizing enzyme-immunoreactive nerves and endocrine cells in the pancreas of the calf and cow was studied immunohistochemically using antisera against tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). TH- and DBH-immunoreactive nerve fibres were abundant both within and around the islet of Langerhans. A few TH- and DBH-immunoreactive nerve fibres were seen around the large islets characteristic of calf pancreas, but the majority of cells in the large islets, and some in islets of Langerhans, showed TH immunoreactivity. In the exocrine pancreas, both TH- and DBH-immunoreactive nerve fibres were distributed randomly among the acini, with the DBH-immunoreactive fibres being more numerous. Abundant TH- and DBH-immunoreactive nerve fibres were seen in close association with blood vessels and in the connective tissue around the interlobular duct. Immunoreactivity for both enzymes was also observed in the nerve cell bodies and fibres of the intrapancreatic ganglia. The findings suggest an important role for catecholamines in the regulation of bovine pancreatic function.     

Morphologic and immunocytochemical study of young dogs with diabetes mellitus associated with pancreatic islet hypoplasia

In 11 dogs (7 males, 4 females; 10 purebred, 1 mixed breed), diagnosed as having diabetes mellitus before the age of 6 months, the pancreas was evaluated histologically; in 6, the pancreas also was examined by use of electron microscopy and/or immunocytochemical methods. Each dog was placed in 1 of 3 groups (A through C) on the basis of pancreatic histopathologic findings: Group A (n = 3)--no recognizable islets, but the pancreas in 2 dogs contained scattered endocrine cells detectable by use of immunoperoxidase staining or electron microscopy; Group B (n = 4)--no recognizable islets, but the pancreas had severe vacuolation of ducts and acini, as well as acinar atrophy; Group C (n = 4)--scant shrunken islets; 1 pancreas had reduced numbers of recognizable islets, hydropic beta-cell vacuolation attributable to glycogen deposition, and islet and nonislet endocrine cells in expected proportions. Insulitis was not observed in any pancreas, although scattered lymphocytes were seen in the pancreatic interstitial fibrous tissue of 3 dogs. Histologic pancreatic lesions in these young dogs were distinct from those of type-I (insulin-dependent) diabetes mellitus in human beings, as well as from those of diabetes mellitus in aged dogs, but were similar to those described in other young diabetic dogs. This uncommon syndrome is distinct from commonly recognized canine diabetes mellitus, on the basis of age of onset, predisposition for purebred dogs, lack of predisposing endocrinopathies or obesity, and pancreatic histologic features. The cause(s) is unknown, but is related to pancreatic endocrine hypoplasia and not to insulitis or to exocrine pancreatic inflammation. The term pancreatic islet hypoplasia is chosen as best describing this disorder.