A Case of Alpha-cell Nesidioblastosis and Hyperplasia with Multiple Glucagon-producing Endocrine Cell Tumor of the Pancreas / 대한소화기학회지

Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.

Beneficial effect of GABA on experimentaly induced diabetes in CD1 mice

Gama amino butyric acid [GABA] is the major inhibitory neurotransmitter in the mammalian nervous system. Pancreatic beta cells in islets of Langerhans express GABA at the levels comparable to those encountered in the central nervous system. The concentrations of GABA and the number of GABA secreting cells, decrease in diabetic patients and experimental diabetes models. Reports on effects of GABA on insulin secretion have been controversial. In this study we investigated whether or not GABA administration in an animal diabetes model can change insulin and glucagon secretion and improve diabetic symptoms. Seven-week old CD1 mice were used. For inducing diabetes, 40 mg/kg of streptozotocin [STZ] was given intraperitoneally for 5 days. Two months after diabetic induction, animals were divided into two groups, one receiving 200 ?mol of GABA, while the other group received phosphate buffer solution [PBS] for two and half months. After 42 days, the glucose concentration in the GABA treated group decreased significantly compared to the untreated group and the first day. After two and half months, water consumption in the GABA treated group decreased significantly in comparison to the control group. Plasma insulin level increased significantly [0.989 +/- 0.67 vs 0.779 +/- 0.11] while plasma glucagon level decreased significantly [91.71 +/- 4.52 vs 130.07 +/- 18.78]. Glucose tolerance test in the GABA group returned to normal levels. GABA administration by regulation of insulin and glucagon secretion could help treat some diabetic symptoms, and could possibly be used in the future as a therapeutic tool in diabetes

Decrease in intestinal endocrine cells in Balb/c mice with CT-26 carcinoma cells

The density of intestinal endocrine cells, in Balb/c mice with colon 26 (CT-26) carcinoma cells, were examined immunohistochemically at 28 days after implantation. After CT-26 cell administration there was a significant decrease in most of the intestinal endocrine cells (p < 0.01) compared with the control group. The significant quantitative changes in the intestinal endocrine cell density might contribute to the development of the gastrointestinal symptoms commonly encountered in cancer patients.

Immunocytochemical study of the distribuition of endocrine cells in the pancreas of the Brazilian sparrow species Zonotrichia Capensis Subtorquata (Swaison, 1837)

In the present study, we investigated types of pancreatic endocrine cells and its respective peptides in the Brazilian sparrow species using immunocytochemistry. The use of polyclonal specific antisera for somatostatin, glucagon, avian pancreatic polypeptide (APP), YY polypeptide (PYY) and insulin, revealed a diversified distribution in the pancreas. All these types of immunoreactive cells were observed in the pancreas with different amounts. Insulin- Immunoreactive cells to (B cells) were most numerous, preferably occupying the central place in the pancreatic islets. Somatostatin, PPA, PYY and glucagon immunoreactive cells occurred in a lower frequency in the periphery of pancreatic islets.

Os tipos de células endócrinas e seus respectivos peptídeos reguladores foram estudados imunocitoquimicamente no pâncreas do tico-tico, espécie Zonotrichia capensis subtorquata, empregando-se o método imunocitoquímico ABC - Peroxidase (Complexo Avidina - Biotina - Peroxidase) e anti-soros específicos para somatostatina, ao glucagon, ao polipeptídeo pancreático aviário (PPA), ao polipeptídeo YY (PYY) e à insulina. Todos estes tipos de células imunorreativas foram observadas no pâncreas em quantidades diferentes. As células imunorreativas à insulina (células B) foram as mais numerosas, ocupando preferencialmente, a região central das ilhotas pancreáticas. As células endócrinas imunorreativas à somatostatina, PPA, PYY e glucagon localizaram-se predominantemente na periferia das ilhotas.

Insulin and Glucagon Secretions, and Morphological Change of Pancreatic Islets in OLETF Rats, a Model of Type 2 Diabetes Mellitus

This study was performed to observe the changes of glucose-related hormones and the morphological change including ultrastructure of the pancreatic islets in the male Otsuka Long-Evans Tokushima Fatty rat. Area under the curve (AUC) of glucose at the 30th (709 +/- 73 mg.h/dL) and at the 40th week (746 +/- 87 mg.h/ dL) of age were significantly higher than that at the 10th week (360 +/- 25 mg.h/ dL). AUC of insulin of the 10th week was 2.4 +/- 0.9 ng.h/mL, increased gradually to 10.8 +/- 8.3 ng.h/mL at the 30th week, and decreased to 1.8 +/- 1.2 ng.h/mL at the 40th week. The size of islet was increased at 20th week of age and the distribution of peripheral alpha cells and central beta cells at the 10th and 20th weeks was changed to a mixed pattern at the 40th week. On electron microscopic examination, beta cells at the 20th week showed many immature secretory granules, increased mitochondria, and hypertrophied Golgi complex and endoplasmic reticulum. At the 40th week, beta cell contained scanty intracellular organelles and secretory granules and apoptosis of acinar cell was observed. In conclusion, as diabetes progressed, increased secretion of insulin was accompanied by increases in size of islets and number of beta-cells in male OLETF rats showing obese type 2 diabetes. However, these compensatory changes could not overcome the requirement of insulin according to the continuous hyperglycemia after development of diabetes.

Immunohistochemical Study of the Endocrine Cells in the Pancreas of the Carp,Cyprinus carpio (Cyprinidae)

The regional distribution and relative frequency of some endocrine cells in the pancreas of the carp, Cyprinus carpio Linnaeus, belonging to the family Cyprinidae in the order Cypriniformes, were observed using specific mammalian antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP) by peroxidase antiperoxidase (PAP) method. The pancreas was divided into four regions (principal and secondary islets, exocrine and pancreatic duct regions). In addition, the pancreatic islet regions were further subdivided into three regions (central, mantle and peripheral regions) and the pancreatic duct regions were subdivided into two regions (epithelial and subepithelial regions). Spherical to spindle or occasionally round to oval shaped immunoreactive (IR) cells were demonstrated in the pancreatic islets, exocrine and pancreatic duct. In the principal islet regions, some cells were also detected in the other regions, most of insulin- and somatostatin-IR cells were located in the central regions, and glucagon- and hPP-IR cells were situated in the peripheral regions. In this regions, insulin-IR cells were most predominant cell types and then, glucagon, somatostatin and hPP in that order. In the secondary islet regions, the regional distribution and relative frequency of these four types of endocrine cells were quite similar to those of the principal islets except for cell clusters consisted of hPP-IR cells that were situated in the peripheral to mantle regions. In the pancreatic duct regions, all four major pancreatic endocrine cells were demonstrated in the inter-epithelial cells and/or basal regions of the epithelial linning. In addition, cell clusters composed of numerous insulin-, moderate glucagon- and somatostatin-IR cells of low frequency were also observed in the subepithelial regions of the pancreatic duct. In the exocrine regions, insulin-, glucagon-, somatostatin- and hPP-IR cells were located in the inter-acinus regions with rare, a few, moderate and moderate frequencies, respectively. In conclusion, the regional distribution and relative frequency of four major pancreatic endocrine cells, insulin-, glucagon-, somatostatin- and hPP-IR cells, in the pancreas of the carp showed general patterns which were observed in other stomachless teleost. However, some species- dependent different distributional patterns and/or relative frequencies were also demonstrated.

An immunohistochemical Study on the Pancreatic Endocrine Cells of the C57BL/6 Mouse

The regional distribution and relative frequency of the pancreatic endocrine cells in the C57BL/6 mouse were studied by immunohistochemical method using four types of specific mammalian antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (PP). The pancreas of mouse could be divided into three portions; pancreatic islets, pancreatic duct and exocrine portions, and pancreatic islets were further subdivided into three regions (central, mantle and peripheral regions) according to their located types of immunoreactive cells and pancreatic duct portions were also subdivided into two regions (epithelial and connective tissue regions). In the pancreatic islet portions, although some cells were also demonstrated in the mantle regions, most of insulin-immunoreactive cells were located in the central regions and they were randomly dispersed in the whole pancreatic islets. Glucagon-immunoreactive cells were detected in the mantle and peripheral regions. Their relative frequencies in the peripheral regions were somewhat numerous than those of the mantle regions. Somatostatin-immunoreactive cells were detected in the mantle and peripheral regions. However, no PP-immunoreactive cells were demonstrated in the pancreatic islets of C57BL/6 mouse. In the pancreatic duct portions, rare glucagon-immunoreactive cells were situated in the epithelial regions. Cell clusters that consisted of glucagon- or somatostatin- immunoreactive cells were found in some case of connective tissue regions of pancreatic ducts. However, insulin- and PP-immunoreactive cells were not detected in the epithelial nor connective tissue regions. In the exocrine portions, all four types of immunoreactive cells except for PP cells were demonstrated in the C57BL/6 mouse. However, no PP-immunoreactive cells were demonstrated. In conclusion, regional distribution of endocrine cells in the pancreas of C57BL/6 mouse was similar to that of mammals, especially other rodents except for topographically different distribution of endocrine cells compared to that of other rodents.

Immunohistochemical Study of the Pancreatic Endocrine Cells in the BALB/c mice: An Unique Distributional Pattern of Glucagon

The regional distribution and relative frequency of insulin-, glucagon-, somatostatin- and pancreatic polypeptide (PP)-producing endocrine cells in the pancreas of BALB/c mouse were investigated by immunohistochemical method. The pancreas of mice was divided into two portions; pancreatic islets and exocrine portions, and pancreatic islets were further subdivided into two regions (central and peripheral regions) and the relative frequency and regional distribution of immunoreactive cells against insulin, glucagon, somatostatin and PP antisera were monitored. In the pancreatic islet portions, insulin-immunoreactive cells were located in the central regions and they were randomly dispersed in the whole pancreatic islets in some case of the small islets. Quite different from those of other mammals, glucagon-immunoreactive cells were dispersed throughout central to peripheral regions in case of large islets and in the smaller ones, most of these cells were situated in the peripheral regions. Somatostatin-immunoreactive cells were detected in the peripheral regions with various frequencies. Although some cells were demonstrated in the central regions of pancreatic islets, most of PP-immunoreactive cells were located in the peripheral regions. In the exocrine portions, all four types of immunoreactive cells were demonstrated in the BALB/c mouse. Some peculiar distributional patterns of pancreatic endocrine cells were found in BALB/c mouse, especially in case of glucagon-immunoreactive cells.

Regional Distribution and Relative Frequency of Gastrointestinal Endocrine Cells in Large Intestines of C57BL/6 Mice

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the three portions (cecum, colon and rectum) of the large intestinal tract of C57BL/6 mice were examined with immunohistochemical method using 7 types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecyctokinin (CCK)-8. In this study, all 3 types of immunoreactive (IR) cells were identified. Most of these IR cells in the large intestinal portion were generally spherical or spindle in shape (open-typed cell) while cells with a round shape (close-typed cell) were found in the intestinal gland. Their relative frequencies varied according to each portion of the large intestinal tract. CGA-IR cells were found throughout the whole large intestinal tract but were most predominant in the colon. Serotonin-IR cells were detected throughout the whole large intestinal tract and showed highest frequency in the colon. Peculiarly, glucagon-IR cells were restricted to the colon with a low frequency. However, no somatostatin-, HPP-, gastrin- and CCK-8-IR cells were found in the large intestinal tract. In conclusion, some peculiar distributional patterns of large intestinal endocrine cells were identified in C57BL/6 mice.

Papel del Páncreas en el Asma Bronquial / Role of the pancreas in bronchial asthma

El asma bronquial tiene alta prevalencia al nivel mundial y a pesar de los grandes esfuezos que se hacen, la mortalidad por esta causa ha aumentado y su verdadera razón se desconoce. En la presente revisión presentamos evidencias de la participación de las hormonas pancreáticas, insulin y glucagón, en la fisiopatología del asma bronquial. Se plantea la hipótesis de que debido al efecto proinflamatorio de la insulina y antiinflamatorio del glucagón, las alteraciones en las concentraciones plasmáticas de esta hormona podrían ser importantes en la evolución del asma bronquial. Se discute el posible papel deleterio de los tratamientos antiasmáticos clásicos por su influencia sobre estas hormonas y se sugieren investigaciones que pudieran aportar luz a los conocimientos actuales

Maintenance of pancreatic endocrine B cells of neonatal rat: Part-XIV--Effect of maternal hyperglycemia on the secretion of insulin and glucagon.

Effects of gestational hyperglycemia on A and B cells were examined in pancreatic monolayer islet cell cultures of neonatal rats from mothers of normoglycemia (C) and made slightly (SH), moderately (MH) and highly hyperglycemic (HH) by streptozotocin injection. Monolayer cultures were maintained for 7 days in the medium with 5.5 mM glucose plus 1 mM 2-deoxyglucose. On day 0, B cells of the SH group were more responsive to glucose and 2-ketoisocaproate than those of other groups. On day 7, the response of B cells in the C and SH groups was remarkably enhanced, thus displaying a dose-dependent increasing pattern of insulin secretion in response to glucose, 2-ketoisocaproate and arginine, and a convex-type secretion to leucine. However, there was no response by B cells in the MH and HH groups. Further, a dose-dependent inhibition of glucagon secretion due to glucose was seen in A cells of the C and SH groups on day 0 and day 7. The responses of these A cells to other nutrients were slightly decreased or were of a low convex-type. In the MH group, however, the glucagon secretion was remarkably enhanced due to leucine and 2-ketoisocaproate on day 0 and day 7, and due to arginine on day 7, although it remained suppressed by glucose. A cells of the HH group were unresponsive through the whole culture period. These results suggest that the development of A- and B-cell responses in vitro of neonates was differently affected by the degree of maternal hyperglycemia.

Glucagon secretion and alpha-cell sensitivity to somatostatin in genetically diabetic mice C57BL/KsJ-mdb

En estudios previos en ratones C57BL/ KsJ mdb/mdb, observamos alteraciones en la secreción de insulina inducida por glucosa, y un menor efecto inhibitorio de la somatostatina sobre la secreción de insulina. En el presente trabajo se estudiaron los patrones de secreción de glucagon bajo estimulación con arginina-glucosa, en perfusión de cortes de páncreas de ratones con diabetes genética de 20 a 90 días de vida. También se investigó si las células alfa presentaban una disminuida sensibilidad a la somatostatina. Los resultados muestran que: a) en ratones mdb/mdb de 20 a 90 días, los patrones de secreción de glucagon presentan hipersecreción basal y un primer pico disminuido; b) la somatostatina inhibe la secreción estimulada de glucagon por debajo de los valores basales en ratones mdb/mdb de 20 a 30 días de edad. En estadios posteriores (40 a 90 días de vida), la somatostatina ejerce un menor efecto inhibitorio, ya que los niveles de glucagon permanecen por en cima de los valores basales. Esto puede indicar un progresivo deterioro en la sensibilidad de las células alfa a la somatostatina, hecho que fue previamente observado para las células beta

Acción inhibitoria selectiva del análogo D5-F-TrP8-D-Cys14 somatostatina sobre la liberación de insulina, hormona del crecimiento y glucagon, inducida con arginina en individuos normales / Selective inhibitory effect of the analog D5-F-TrP8-D-Cys14 somatostatin on the arginine induced release of insulin, growth hormone and glucagon, in normal human beings

Se estudió en un grupo de individuos normales la acción de varias dosis de somatostatina y del análogo D5-F-TrP8-D-Cys14-SS sobre la liberación inducida por arginina de insulina, glucagon y hormona de crecimiento (HC). La somatostatina en dosis de 100 g/h suprimió la liberación de insulina, glucagon y HC. El análogo D5-F-TrP8-D-Cys14-SS en dosis de 10 a 20 g/h inhibió a la HC y al glucagon, pero no a la insulina. Estos resultados muestran que es posible obtener análogos de la somatostatina que supriman en forma selectiva a la liberación de insulina, lo que puede ser de gran valor clínico en el manejo de diabetes mellitus, acromegalia, pancreatitis y úlcera péptica

Investigations on metabolic alterations in laying hens following amino acid administration.

Ketogenic amino acids L-leucine and L-isoleucine were administered in amounts of 100 mg with or without 1.5 g glucose to overnight fasting laying hens. On administering leucine the blood glucose level was observed to be slightly reduced while administration of isolencine increased the blood sugar. On injecting leucine or isoleucine with glucose blood glucose level was found to be appreciably higher as compared to that observed on administering glucose alone. In vivo administration of amino acids caused only a slight increase in plasma alpha-amino nitrogen. The liver glycogen was found to be reduced after the administration of amino acids. these observations indicate that amino acids leucine and isoleucine exercise a definite role on glucose uptake, and its mechanism of utilization in poultry birds is different from mammals.