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PubMed1994

Endocrine cells in the rat pancreatic and bile duct system: alteration in diabetes.

Endocrine cells of the pancreatic and bile duct system of the diabetic rat were characterized with reference to their influence on duct function. In streptozotocin-induced diabetic rats, the endocrine cells showed various changes in number and topographic distribution along the epithelial lining of the duct system. With the exception of insulin cells, which demonstrated a marked decrease, the number of duct endocrine cells generally increased in the duct system of the diabetic animal, particularly in the terminal portion of both the common hepatic and the accessory pancreatic ducts encompassed by the muscle sphincters. Among them, the cells secreting somatostatin, a potential peptide inducing contraction of the muscle sphincter, showed a remarkable increase in the opening portion of the common hepatic and the accessory pancreatic ducts of the diabetic animal. The duct cells producing glucagon and pancreatic polypeptide, the hormones exerting an inhibitory effect on exocrine secretion of duct and acinar cells, also increased significantly in the duct system of the diabetic animal. These results suggest that the duct endocrine cells are closely related, not only to functional properties of the duct system, but also to disorders of the pancreas and biliary tract in diabetes.

Animals↗
PubMed2001

Characterization of secretory and morphologic properties of primary cultured endocrine cells from porcine pancreata.

We characterized morphologic and secretory properties of porcine pancreatic endocrine cells in primary culture obtained by autolytic preparation without any exogenous proteolytic enzymes. The endocrine cells exhibited a neuron-like shape, and insulin granules were accumulated at the terminal of the processes. Thus derived endocrine cells survived in culture medium containing nicotinamide and remained sensitive to glucose for at least 6 weeks after preparations. The cells responded well to physiologic concentrations of glucose, and high K+ depolarization and the antidiabetic sulfonylureas, tolbutamide, and glibenclamide also elicited the release. With high glucose, insulin release was markedly potentiated by forskolin, glucagon, glucagon-like peptide-1, and arginine and inhibited by somatostatin, the Ca2+ channel blocker nitrendipine, and the ATP-sensitive K+ channel opener diazoxide. Epinephrine had dual effects on the release by glucose; enhanced within a low nanomolar range and inhibited at 1 micromol/L. However, the cells were unresponsive to leucine. Such secretory sensitivities to nutrients, hormones, and pharmacologic agents, and long survival rate (as long as 5-6 weeks) of these cells suggest to us therefore that derived endocrine cells may be useful for xenotransplantation of pancreatic beta cells for treatment of insulin-dependent diabetes mellitus.

Animals↗
PubMed1991

Endocrine cell carcinoma of the gallbladder.

An endocrine cell carcinoma in the gallbladder of a 59-year-old woman is reported. The morphological features of this diagnosis are compared with 14 previously reported primary gallbladder carcinoid tumours that had metastasized. The histogenesis and current classification of endocrine cell tumours is discussed.

Adenocarcinoma, Scirrhous↗
PubMed2005

Ex vivo analysis of acinar and endocrine cell development in the human embryonic pancreas.

In contrast to the considerable body of data on pancreas development in rodents, information on pancreas development in humans is scant. We previously described a model in which mature beta cells developed from human embryonic pancreas: human embryonic pancreas was grafted under the kidney capsule of scid mice, beta cells were then seen to develop in the graft. Here, we showed that not only beta cells, but also other endocrine cells, acinar cells and ducts develop in this model. We then used this model to probe the mechanisms underlying acinar and beta cell development in the human embryonic pancreas. BrdU pulse/chase experiments produced evidence of clonal acinar cell development: the first acinar cells to appear proliferated, thereby expanding the acinar cell population. In contrast, beta cell development was regulated by the proliferation of pancreatic progenitor cells, followed by beta-cell differentiation. We then showed that early progenitors expressing PDX1 proliferated, whereas late endocrine progenitors expressing Ngn3 did not. This proliferative capacity of early endocrine progenitor cells in embryonic human pancreas may hold promise for obtaining human beta-cell expansion.

Animals↗
PubMed1975

Argentaffin granules in endocrine cells in human duodenal mucosa.

An attempt was made to gain ultracytochemical characteristics of the endocrine cells in the human duodenal mucosa. Bodian argyrophil and Fontana-Masson argentaffin reactions were applied to the blocks of the tissue. The ultracytochemistry showed that the secretion granules of all morphological types of the endocrine cells were precipitated with both the argyrophil and argentaffin silver grains in varying intensity. The endocrine cells containing uniformly round secretion granules tended to show a heavy precipitation with the argyrophil silver grains in contrast to a light precipitation with the argentaffin silver grains. The endocrine cells containing pleomorphic secretion granules were heavily precipitated with both the argyrophil and argentaffin silver grains. The findings of the present study suggest that the duodenal endocrine cells represent a single cell type in respect to 5-hydroxytryptamine metabolism, but differ in their metabolism of other polypeptide hormones.

Chromaffin System↗
PubMed1999

Endocrine cells in the upper gastrointestinal tract in relation to gastrointestinal dysfunction in patients with familial amyloidotic polyneuropathy.

Gastrointestinal (GI) dysfunction is a common complication of familial amyloidotic polyneuropathy (FAP). In previous reports, a decreased content of small and large intestinal endocrine cells has been found in patients with FAP and it has been suggested that this may contribute to the development of GI disturbances. The aim of the present study was to investigate the endocrine cell content in the stomach and duodenum of FAP patients, and to correlate the findings with gastric emptying. Fifteen patients with FAP were included in the study. Twenty-eight subjects with macroscopically and histologically normal mucosa were used as controls for endocrine cell contents and 14 healthy subjects for gastric scintigraphy. The endocrine cells were identified by immunohistochemistry and quantified with image analysis. Gastric emptying time was detected by scintigraphy and endoscopy. The number of chromogranin A-immunoreactive (IR) cells was reduced in all investigated parts of the GI tract except bulbus duodeni. Gastrin/CCK cell content was reduced in duodenum, but tended to be increased in antrum of the stomach (P = 0.07). Otherwise, the content of all other endocrine cells types in the upper GI tract was reduced compared with controls. A correlation with malnutrition was found for gastric inhibitory polypeptide and secretin cell content in bulbus duodeni. Gastric scintigraphy disclosed delayed gastric emptying of solid food, but the finding was not correlated to the decreased content of neuroendocrine cells. The severity of endocrine cell depletion was not correlated to duration of GI disturbances. The present study showed that the endocrine cells of the stomach are affected in FAP patients and that the abnormalities in the upper GI endocrine cells occur early during the course of the disease.

Adult↗
PubMed1993

Endocrine cells in diffuse pulmonary fibrosis.

BACKGROUND: There is evidence to suggest, particularly from studies in animals, that the products of pulmonary endocrine cells, especially gastrin releasing peptide, may have a role in the pathogenesis of fibrosis in the lung. This study was carried out to examine the morphology, number, distribution, and content of pulmonary endocrine cells in tissue from 49 patients with diffuse pulmonary fibrosis. METHODS: Twenty patients with interstitial pneumonitis, 17 with early fibrosis, and 12 with frank honeycombing were studied, together with five age matched controls without pulmonary disease. Endocrine cells were immunolabeled by the avidin-biotin complex method for two general markers (protein gene product 9.5 and neuron specific enolase) and a range of normal and aberrant secretory products. RESULTS: In the early stages, characterised by vigorous pneumonitis, endocrine cells were normal in appearance and distribution but very few in number. They contained only those secretory products normally found in such cells in health; inappropriate substances were not seen. By the time of early fibrosis endocrine cells were even fewer. None were identifiable in the lungs affected by honeycombing, despite the fact that all contained intact, well preserved epithelium. CONCLUSIONS: It seems unlikely that the products of pulmonary endocrine cells can have any role in the pathogenesis of diffuse pulmonary fibrosis in man, the diminution in their number with advancing fibrosis probably reflecting their loss simply as a consequence of generalised epithelial damage.

Cell Count↗
PubMed1986

Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies.

Antibodies to histamine were used to examine the localization of the amine in cells of the stomach and upper small intestine of a great variety of species, including cartilaginous and bony fish, amphibia, reptiles (lizard), birds (chicken) and a large number of mammals. In all species gastric histamine was localized in endocrine cells (invariably found in the epithelium) and mast cells (usually with an extra-epithelial localization). The endocrine cells were identified as such by immunostaining with antibodies to chromogranin A and the mast cells were identified by toluidine blue staining. Histamine-immunoreactive endocrine cells were found almost exclusively in the acid-producing part of the stomach; only rarely were such cells observed in the pyloric gland area. They were fairly numerous in the gastric mucosa of the two subclasses of fish as well as in the amphibia and reptile species studied. Here, the majority of the histamine-immunoreactive endocrine cells seemed to have contact with the gastric lumen (open type cells) and were located in the surface epithelium (certain fish only) or together with mucous neck cells at the bottom of the pits. In the chicken, histamine-immunoreactive endocrine cells were numerous and located peripherally in the deep compound glands. They were without contact with the lumen (closed type) and had long basal extensions ("paracrine" appearance), running close to the base of the oxyntic-peptic cells. In mammals, the number of histamine-immunoreactive endocrine cells in the stomach varied greatly. They were particularly numerous in the rat and notably few in the dog, monkey and man. In all mammals, the histamine-immunoreactive endocrine cells were of the closed type and located basally in the oxyntic glands. They often had a "paracrine" appearance with long basal processes. Histamine-storing mast cells, finally, were few in both subclasses of fish as well as in the amphibian species and in the lizard. They were fairly numerous in chicken proventriculus (beneath the surface epithelium), few in the oxyntic mucosa of mouse, rat and hamster, moderate in number in hedgehog, guinea-pig, rabbit, pig and monkey, and numerous in cat, dog and man.(ABSTRACT TRUNCATED AT 400 WORDS)

APUD Cells↗
PubMed2000

Adeno-endocrine cell carcinoma of the gallbladder.

We encountered a rare case of adeno-endocrine cell carcinoma of the gallbladder in an 81-year-old woman. Imaging study revealed a common bile duct stone. Endoscopic sphincterotomy was performed, and the stone was extracted successfully. Thereafter, cholecystectomy was performed. A papillary tumor was found in the neck of the gallbladder. Histologically, the tumor consisted of two components, well differentiated adenocarcinoma and endocrine cell carcinoma. However, no clinical signs of tumor hormonal activity were observed. The tumor cells in the area of the endocrine cell carcinoma were small and round. Histochemical studies of these tumor cells were positive for chromogranin A and Grimelius silver impregnation. The tumor cells in the area of the adenocarcinoma were well differentiated adenocarcinoma and included goblet-type cells with a tubular structure or solid growth pattern. These adenocarcinoma cells stained positively for Alcian blue and periodic acid-Schiff, and both types of tumor cells stained positively for carbohydrate antigen and carcinoembryonic antigen. It was suggested that the histogenesis of the endocrine cell carcinoma of the gallbladder was closely related to that of the adenocarcinoma.

Adenocarcinoma↗
PubMed1987

Hyperplastic lesions of the gastrointestinal endocrine cells.

A substantial body of knowledge is presently available on the morphologic, histochemical, ultrastructural, and functional characteristics of both the normal endocrine cell population of the gut and their related endocrine tumors. In contrast to this, we have only recently begun to recognize the existence of hyperplastic proliferations of various endocrine cell types, and information is therefore steadily accumulating on the morphologic criteria for their recognition, their clinicopathologic correlates and the clinical relevance of this morphologic finding. Hyperplastic proliferations of various endocrine cell types most often develop as a secondary phenomenon in a variety of clinical situations, and may modify the clinical course of the associated condition in a manner that underscores the functional interrelationships these endocrine cells have not only with each other but with other cell types as well. However, similar proliferations may also occur as a primary event (e.g. primary antral G-cell hyperplasia) and give rise to clinical and biochemical features attributable to the overproduction of their specific hormonal product (e.g. Zollinger-Ellison Syndrome, type I). This communication provides a broad overview of the current state of our knowledge of hyperplastic lesions of a variety of gut endocrine cell types in humans, their pathophysiologic significance, their relationship (if any) to the subsequent development of endocrine tumors (i.e. the hyperplasia-neoplasia sequence), and the utility of certain experimental models for the study of such proliferations in a variety of animal species.

APUD Cells↗
PubMed1999

Colonic endocrine cells in patients with familial amyloidotic polyneuropathy.

OBJECTIVE: To establish whether the endocrine cell number is affected in the colon in Japanese FAP patients. SETTING: Department of Medicine, Umeå University Hospital and Department of Internal Medicine and Pathology, University Hospital, Kumamoto, Japan. SUBJECTS: Autopsy colon tissue specimens from 11 FAP patients and nine controls as well as 12 control biopsy specimens were included in the study. MEASUREMENTS: Endocrine cells in the colon were detected by immunohistochemistry and quantified by computerized image analysis. RESULTS: The autopsy material showed a slight autolysis. Neither enteroglucagon nor pancreatic polypeptide positive cells could be detected in the autopsy material, but were present in biopsy material. There was no statistical difference between autopsy and biopsy specimens regarding the number of peptide YY (PYY), somatostatin and serotonin cells. No significant differences were noted in PYY, somatostatin and serotonin immunoreactive cells in FAP patients compared to autopsy controls, though PYY cells tended to be decreased and serotonin and somatostatin cells tended to be increased in FAP patients. CONCLUSION: The difference between the Swedish and Japanese patients in the endocrine cell content points to the possibility of involvement of other factors than the endocrine cell depletion of the colon might be involved in the pathogenesis of gastro-intestinal dysfunction in FAP. The tendency of PYY to decrease in Japanese FAP might contribute to the development of diarrhoea in these patients.

Adult↗
PubMed2001

Pantoprazole therapy in the long-term management of severe acid peptic disease: clinical efficacy, safety, serum gastrin, gastric histology, and endocrine cell studies.

OBJECTIVE: Pantoprazole is the third proton pump inhibitor to become available. When this study was started, there were few data on its long-term use. Our aim was to investigate this aspect and, because powerful inhibitors of acid secretion can cause hypergastrinemia and, in experimental animals, enterochromaffin-like cell hyperplasia, we also monitored serum gastrin and endocrine cell histology. METHODS: One hundred fifty patients refractory to H2-receptor antagonists, running an aggressive course or with complications, were entered into a 5-yr treatment program. We performed serial endoscopy, checked for adverse events, and laboratory values. We also monitored serum gastrin, gastric endocrine cell histology, and antral and corpus gastritis. RESULTS: This report presents results from up to 3 yr of treatment. Cumulative healing on 40-80 mg of pantoprazole was 82% at 4 wk and 92% by 12 wk. Most patients became asymptomatic within 4 wk. Remission on maintenance treatment with 40 mg (n = 111) was 85% at 12 months and 78% at 24 months. Treatment was safe; only four patients had adverse events definitely related to pantoprazole. Elevations in gastrin were modest and there were no significant changes in gastric endocrine cells. The number of enterochromaffin-like cells tended to decrease. CONCLUSION: Pantoprazole is effective, safe, and does not seem to be associated with large increases in serum gastrin or alterations in gastric endocrine cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Immunocytochemical and ultrastructural characterization of endocrine cells and nerves in the intestine of Rana temporaria.

Endocrine cells have been identified in the intestine of the frog Rana temporaria after application of the Grimelius and Masson-Fontana techniques. These endocrine cells were examined using immunocytochemical techniques on paraffin and semithin sections for light microscopy. After testing 19 antisera, 12 immunoreactivities were identified. Numerous serotonin-, somatostatin- and GLP-1-immunoreactive cells; a moderate number of PYY-, glucagon-, VIP-, gastrin/CCK-immunoreactive cells and few human PP-, bombesin-, substance P- and neurotensin-immunoreactive cells were found. VIP- and met-enkephalin were identified in nerve fibers of the muscular layer. Using semithin-thin sections five types of endocrine cells (serotonin-, somatostatin-, gastrin/CCK-, glucagon- and bombesin-immunoreactive cells) have been characterized according to their immunocytochemical reaction and the ultrastructure of the secretory granules.

APUD Cells↗
PubMed2005

Changes of the gastric endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma: an immunohistochemical quantitative study.

AIM: The regional distributions and relative frequencies of some gastric endocrine cells of C57BL/6 mice were studied by immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon and human pancreatic polypeptide (HPP) after subcutaneous implantation of murine lung carcinoma (3LL) cells. METHODS: The experimental animals were divided into two groups, one is non-implanted sham and the other is 3LL-implanted group. Samples were collected from the two regions of stomach (fundus and pylorus) at 28 d after implantation of 3LL cells (1 x 10(5) cell/mouse). RESULTS: In this study, all the seven types of immunoreactive (IR) cells were identified except for HPP. Most of these IR cells in the gastric portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found occasionally. The regional distributions of gastric endocrine cells in the 3LL-implanted group were similar to those of non-implanted sham. However, significant decreases of some types of IR cells were detected in 3LL-implanted group compared to those of non-implanted sham. In addition, the IR cells showing degranulation were numerously detected in 3LL-implanted group. CGA-, serotonin- and somatostatin-IR cells in the fundus and pylorus regions, and gastrin-IR cells in the pylorus regions of 3LL-implanted groups significantly decreased compared to those of non-implanted sham. However, no changes on frequencies of CCK-8- and glucagon-IR cells were demonstrated between 3LL-implanted and non-implanted groups. CONCLUSION: Endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. Implantation of tumor cell mass (3LL) induced severe quantitative changes of gastric endocrine cell density, and the abnormality in density of gastric endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

Animals↗
PubMed1979

Emiocytotic granule release without intraluminal stimulus in human colonic endocrine cells of fetuses, children and adults.

In endocrine cells of the colon of adults, children and fetuses, exocytotic granule release without any specific stimulation is reported. Omega-invaginations are observed on both the lateral and basal surfaces of all types of colonic endocrine cells. Several explanations for the phenomenon are suggested: 1) emiocytosis is probably more frequent in the colon than in the proximal gut, this allows its observation without requiring an exogenous stimulus, 2) since most of the exocytotic figures are from anaesthetized subjects it is also assumed that contraction of the muscular layer induced by anaesthetics and the resulting increase in intraluminal pressure were the possible causes of granule release, 3) in non-anaesthetized subjects release may have taken place in response to a normal endogenous physiological stimulus, or to the dilation of colon during colonoscopy. Certain figures on lateral surfaces between endocrine and adjacent cells i.e., bulges of parallel plasma membranes surrounding a secretory granule, were observed. Their significance is unknown.

Adult↗
PubMed2000

Immunohistochemical study on the distribution of endocrine cells in the gastrointestinal tract of the babirusa, Babyrousa babyrussa (Suidae).

The distribution and relative frequency of endocrine cells in the gastrointestinal tract of the babirusa were studied immunohistochemically using the avidin-biotin-peroxidase complex method. Thirteen types of gut endocrine cells were detected; they were immunoreactive for chromogranin, serotonin, somatostatin, gastrin, bovine pancreatic polypeptide (BPP), glucagon, secretin, cholecystokinin (CCK), methionine-enkephalin-Arg6-Gly7-Leu8 (MENK8), motilin, gastric inhibitory polypeptide (GIP) and peptide tyrosine tyrosine (PYY). Cells that were immunoreactive for chromogranin, serotonin, somatostatin and glucagon were found in all portions of the gastrointestinal tract. MENK8-immunoreactive cells were observed in the stomach and small intestine. Gastrin-immunoreactive cells were detected in the pyloric region and duodenum. PYY-immunoreactive cells were found in the small and large intestine. Cells immunoreactive for motilin, CCK, GIP, and secretin were observed in the proximal small intestine and those immunoreactive for neurotensin were found only in the ileum. Although the distribution pattern of endocrine cells in the gastrointestinal tract of babirusa was similar to those reported for pig, restricted distribution of several endocrine cells, gastrin, BPP, MENK8, motilin, CCK, GIP, secretin and neurotensin and wider distribution of glucagon and PYY were observed in the babirusa. The unexpected presence of MENK8 in all glandular regions of the stomach and PYY in the small intestine was also noted. The distribution of gut endocrine cells might be related to the regulatory characteristics of the babirusa digestive tract.

Animals↗
PubMed1999

Postnatal development of intestinal endocrine cell populations in the water buffalo.

The frequency and distribution of 11 endocrine cell populations were studied in the intestine of differently aged buffalo, grouped on the basis of diet: 2-d-olds (suckling), 5-mo-olds (weaning) and 5-y-olds (ruminant adult diet). The endocrine cell populations were identified immunocytochemically using antisera against 5-hydroxytryptamine (5-HT), somatostatin, gastrin, cholecystokinin (CCK), COOH-terminal octapeptide of gastrin/CCK, neurotensin, motilin, gastric inhibitory polypeptide (GIP), secretin, glucagon/glicentin (GLU/GLI) and polypeptide YY (PYY). In adult buffalos the regional distribution of endocrine cells is similar to that of other adult ruminants. During postnatal development, these cell types showed the following changes in their frequency and distribution: (1) 5-HT, neurotensin and gastrin/CCK immunoreactive cells (i.c.) showed a decrease in frequency with age; (2) somatostatin i.c. frequency remained stable with age; (3) motilin, GIP, secretin and CCK i.c. showed a slight increase in frequency with age; (4) GLU/GLI and PYY i.c. decreased in frequency with age in the small intestine, caecum and proximal colon and an increase in frequency in the rectum. It was hypothesised that the endocrine cell types, whose presence and localisation is substantially stable in all examined ages, probably contain substances that are strictly necessary for intestinal function. In contrast the hormones contained in the cell populations that decreased with age, are probably involved in physiological needs during the milk and weaning diet or play a role in intestinal growth.

Aging↗
PubMed1997

Pulmonary endocrine cells in anthracosilicotic lungs.

It has been suggested by some studies of human and animal lungs that the products of pulmonary endocrine cells, particularly gastrin-releasing peptide, might play a role in fibrogenesis, but more recent detailed studies of fibrotic human lungs have failed to confirm this. We have made a detailed quantitative examination of a series of fibrotic human lungs to see if we could determine whether there was any relationship between endocrine cells and fibrosis. Using immunocytochemistry, we investigated the morphology, content, distribution and number of pulmonary endocrine cells in 15 pairs of fibrotic lungs from coal miners, and compared their features with those of equivalent cells in age-matched controls. Proliferation of endocrine cells was seen in the lungs of just two miners, in which it was focal and associated with acute bronchitis and bronchopneumonia. There was no difference between the miners and controls in the appearance (mostly solitary cells), content (predominantly gastrin-releasing peptide and calcitonin), distribution (mainly in small bronchi and bronchioles), or number (4.5 vs 4.1 cells per 10,000 epithelial cells, respectively) of endocrine cells. It seems unlikely that the substances secreted by these cells play any role in stimulating fibrosis in human lungs, but rather that they have a function in the inflammatory response to pulmonary injury.

Aged↗