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PubMed1994

Ablation of islet endocrine cells by targeted expression of hormone-promoter-driven toxigenes.

Ontogenic relationships between the different types of endocrine cells in the islets of Langerhans were explored by generating transgenic mouse embryos in which cells transcribing the glucagon, insulin, or pancreatic polypeptide genes were destroyed through the promoter-targeted expression of the diphtheria toxin A chain. Embryos lacking glucagon- or insulin-containing cells did not exhibit alterations in the development of the nontargeted islet cell types, whereas embryos lacking pancreatic polypeptide gene-expressing cells also lacked pancreatic insulin- and somatostatin-containing cells. These results show that neither glucagon nor insulin gene-expressing cells are essential for the differentiation of the other islet endocrine-cell types. These results also suggest that pancreatic polypeptide gene-expressing cells are indispensable for the differentiation of islet beta and delta cells because the former produce a necessary paracrine or endocrine factor and/or operate through a cell-lineage relationship.

Animals↗
PubMed2005

Composite glandular-endocrine cell carcinoma of the stomach. Report of two cases with goblet cell carcinoid component.

Composite glandular-endocrine cell carcinoma (CGECC) is recognized as a special type of gastric tumor composed of ordinary adenocarcinoma and neuroendocrine tumors. Goblet cell carcinoid (GCC) is a well-established type of appendiceal carcinoid, but the GCC component has not been well delineated in CGECC of the stomach. We report on two gastric CGECCs with a GCC component, analyzing the histologic components by immunohistochemistry. On initial biopsy, both cases were diagnosed as signet-ring cell carcinoma. However, the resected tumors consisted of three components: signet-ring cell carcinoma, GCC, and glandular adenocarcinoma. Although some signet-ring carcinoma cells and goblet carcinoid cells were indistinguishable by hematoxylin and eosin staining, E-cadherin immunostaining disclosed a definitive difference regarding the staining pattern in these cells. Both patients are well, with no recurrent tumor for about 10 years of follow-up. CGECC with a GCC component may have been confused with conventional adenocarcinoma with signet-ring cells. In cases of advanced signet-ring cell carcinoma with good prognosis, the possibility of such CGECC has to be considered.

Adult↗
PubMed1983

Successful intracerebral allotransplantation of purified pancreatic endocrine cells in diabetic rat.

Single pancreatic endocrine cells (PEC) have been demonstrated to restore normoglycemia when transplanted intracerebrally in diabetic rat recipients across a major histocompatibility barrier without immunosuppression. Twelve out of twelve transplants of purified PEC have achieved long-term survival of over 176 days. This approach would provide a model to identify the specific cell(s) as inducer of graft rejection and an opportunity for transplantation study in spontaneous diabetic BB rats and larger diabetic animal models.

Animals↗
PubMed1988

Allotransplantation of dispersed single pancreatic endocrine cells in diabetic rats.

Dispersed pancreatic endocrine cells (PECs) were recently shown to survive indefinitely in the brain of allogeneic diabetic rat recipients across the major histocompatibility barrier without immunosuppression. Purified PECs (2-3 X 10(6) cells) prepared from Wistar rat islets were transplanted in 10 different sites in streptozocin-induced diabetic ACI rats. Blood glucose and body weight changes were monitored throughout the study. PEC isografts (n = 5) and allografts (n = 6) were nonfunctional when transplanted in intramuscular, intravenous, and intrahepatic sites. When transplanted intraportally (n = 6) and intraperitoneally (n = 6), similar grafts were functional but had a short survival period (6.6 +/- 1.5 and 15.3 +/- 16.6 days, respectively). Prolonged graft survival in some recipients was observed when kidney capsule [5, 9, 10, 240, 282, and 300 (2 rats) days], omentum pocket (7, 8, 10, 90, 105, 154, 155, and 157 days), and testis (7, 8, 12, 150, 230, and 234 days) were the transplantation sites. Permanent graft survival was achieved in 20 of 20 recipients with intracerebral transplantation and 21 of 22 recipients with intrathecal transplantation. These findings confirm that dispersed single PECs can be transplanted as a permanent functional graft and can normalize the hyperglycemia of the diabetic recipients. The duration of PEC graft survival is variable and depends on the transplantation site. Both the cerebral cortex and subarachnoid space, which are immunologically privileged sites, have provided the best allograft protection.

Animals↗
PubMed2006

[A case of partial response in liver metastatic lesion from gastric endocrine cell carcinoma treated with TS-1].

Endocrine cell carcinoma (ECC) of the stomach is a rare pathological type with a poor outcome. Standard chemotherapy has not yet been established. We experienced a case of partial response in the liver metastasis from the gastric ECC treated with TS-1. The patient was a 68-year-old female. An upper GI series and gastroendoscopy revealed pyrolus stenosis and CT-scan showed liver metastasis. A non-curative total gastrectomy was performed to allow oral intake. Since the histopathological examination revealed that tumor cells were partially positive for chromogranin A on immunohistochemical study, we diagnosed tumor ECC of the stomach. The patient with liver metastasis was treated using TS-1, and CT-scan showed a remarkable decrease (PR) in the metastatic lesion. TS-1 administration can improve the clinical outcome for ECC of the stomach.

Aged↗
PubMed2005

Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa.

Leptin is a hormone secreted by the gastric mucosa into the lumen of the stomach. It is present in its intact form in the intestine where it regulates nutrient absorption and intestinal mucosa integrity. We have identified the binding protein that protects leptin from the harsh conditions of the gastric juice. Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice, bound to a protein corresponding to the extracellular domain of the leptin receptor. In the absence of this soluble receptor, leptin is rapidly degraded. Immunocytochemistry on rat gastric mucosa identified the cells and intracellular compartments involved in secretion of this complex. Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum-Golgi-granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells. The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells. The shedding of the receptor occurs in the immature granules. It is concluded that in the immature secretory granules of Chief cells, furin activates proprotein convertase 7 that, in turn, cleaves the extracellular portion of membrane-bound leptin receptors. Leptin bound to its soluble receptor forms a complex that is resistant to the gastric juice. Endocrine cells, on the other hand, generate a soluble leptin receptor by mechanisms different from those of the exocrine cells.

Animals↗
PubMed1998

The nature and implication of intestinal endocrine cell changes in coeliac disease.

Coeliac disease is associated with intestinal lesion. This lesion causes architectural derangement of the mucosa in the form of villus atrophy, increased crypt length and increased volume of the lamina propria. Several changes in the intestinal endocrine cells have been reported over the years, e.g. the number of secretin cells and increased numbers of GIP, CCK/gastrin, motilin, and serotonin cells. There is no consensus about the nature of the changes in somatostatin-cells. It has been postulated that the changes in the endocrine cells are a selective process to meet the new demands exerted by the dramatic decrease in intestinal absorptive area. It has been speculated further that the changes in the endocrine cells would cause an incomplete digestion of the ingested food and its rapid elimination from the intestine. These changes may be responsible for the diarrhoea and steatorrhoea that occur in patients with coeliac disease.

Celiac Disease↗
PubMed1987

Coexistence of pancreatic polypeptide (PP)-and glucagon-immunoreactivity in pancreatic endocrine cells of mouse.

Immunocytochemical double staining techniques were used to study PP- and glucagon-like-immunoreactivity in pancreatic endocrine cells of mouse. An antiserum against FMRFamide appeared to react with all PP-immunoreactive endocrine cells. With fluorescence microscopy most PP/FMRFamide-immunoreactive cells also showed glucagon-immunoreactivity, but cells containing only PP- or glucagon-like substances were found as well. The proportion of cells containing PP-, glucagon, and both immunoreactivities varied strongly from islet to islet in all parts of the pancreas. Using an electron microscopical immunogold double staining procedure on Lowicryl-embedded pancreas, PP/FMRFamide- and glucagon-immunoreactivity appeared to be present in the majority of endocrine A cells; both immunoreactivities were randomly distributed within the granules of these cells. Cells containing only PP/FMRFamide- or glucagon-immunoreactivity were also found. Glucagon- and a faint FMRFamide-immunoreactivity was also observed in osmicated epon-embedded tissue. Independent of their immunoreactivity all positive cells showed the same round electron dense secretory granules.

Animals↗
PubMed2001

Morphogenesis of gut and distribution of the progenitors of gut endocrine cells at cranial somite levels of the chick embryo.

The primary objective of this study was to establish the distribution of the progenitors of selected gut endocrine cell types at cranial somite levels. In addition, analysis of the material has provided new information about the location of the presumptive territories of certain gut regions and of the pancreas. Narrow transverse strips of full-thickness blastoderm two or three somites in length were excised at the levels of somites 1 to 5 of 8.5- to 18-somite chick embryos and cultured as chorioallantoic grafts to an age equivalent to 20 days of incubation. The grafts were analysed by immunocytochemistry, and their morphology was evaluated. Individual grafts exhibited up to five different types of gut morphology, including those of oesophagus, proventriculus, gizzard, pyloric region, small intestine, and pancreas. The morphologic survey yielded new information about the location, extent, or both, of the territories of the pyloric region, the small intestine, and the pancreas. In general, the progenitors of gut endocrine cell types identified were those expected for the different morphologic regions: in only a few instances were ectopic endocrine cell types detected. The available evidence points to the progenitors of bombesin/gastrin-releasing peptide cells being located cranial to somite 5 at the stages studied. Based on the morphology and the proportion of insulin cells, the development of pancreas in grafts appeared compromised compared with grafts of the intact dorsal pancreatic bud: this may relate to the likely exclusion of dorsal pancreatic bud mesoderm from the graft area. The results show that presumptive small intestinal endoderm in grafts can differentiate in the absence of homologous (i.e., small intestinal) mesoderm: this accords with the view that the primary source of positional information in the gut is in the endoderm.

Animals↗
PubMed1989

Alteration of pancreatic endocrine cell patterns and their secretion during pancreatic carcinogenesis in the hamster model.

Proliferation of endocrine cells was found to occur during early, i.e., first 12 weeks, exocrine pancreatic carcinogenesis after 6 weekly treatments of Syrian hamsters with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). Cells containing insulin (Ins), glucagon (Glu), and somatostatin (Som) were noted in all stages of tumor development and were present in adenocarcinomas and in metastases to the liver. Some of the cancer cells were of amphicrine (hybrid) type, i.e., produced both mucin and endocrine substances. Measurement of these hormones revealed a significant decrease in plasma Ins during early stages of carcinogenesis with concomitant increase of Ins level in pancreatic juice at 12 weeks after 6 weekly BOP treatments. Plasma Glu and Som were not changed. The changes noted, particularly in relation to Ins, suggest that proliferation of endocrine cells in pancreatic carcinogenesis may be associated with alterations in hormone secretion.

Animals↗
PubMed1990

Gastrin-releasing peptide: neuronal distribution and spatial relation to endocrine cells in the human upper gut.

By using immunocytochemical techniques, we have studied the distribution of gastrin releasing peptide (GRP)-containing neurons as well as the spatial relationship between these neurons and the endocrine cells in the human stomach and duodenum. Moderate numbers of immunoreactive fibers were distributed in the smooth muscle and submucosa of the stomach; they were more rare in the duodenal wall. Numerous GRP-containing nerve fibers were found in the oxyntic mucosa, the antral mucosa harboured only few GRP immunoreactive nerve fibers. The mucosa of the proximal duodenum was found to be virtually devoid of such fibers. Only occasionally did we observe signs of a direct contact between GRP-containing nerve fibers and gastrin and somatostatin cells in the antral mucosa. In the oxyntic mucosa GRP-containing nerve fibers sometimes seemed to contact endocrine cells, including somatostatin cells as well as individual parietal cells. In conclusion, although GRP-containing nerve fibers were quite numerous in the wall of the human upper gastro-intestinal (GI)-tract, we observed a lack of intimate spatial relationship between these fibers and endocrine cells in the antral mucosa, suggesting additive mechanisms to a direct innervation of gastrin cells and somatostatin cells by GRP nerve fibers explaining the physiological effects on hormonal release.

Adult↗
PubMed1984

The distribution of endocrine cell progenitors in the gut of chick embryos.

The aim of this experiment was to find out whether or not, at early stages of development, progenitors of the various types of gut endocrine cells are localized to one or more specific regions of the gastrointestinal tract. Transverse strips of blastoderm two to four somites in length were excised between the levels of somites 5 and 27 in chick embryos at 5- to 24-somite stages and were cultured as chorioallantoic grafts. The distribution of endocrine cells in the grafts revealed confined localization of progenitor cells only in the case of insulin-immunoreactive cells. The progenitors of cells with somatostatin-, pancreatic polypeptide-, glucagon-, secretin-, gastrin/CCK-, motilin-, neurotensin- and serotonin-like immunoreactivity were distributed along the length of the presumptive gut at the time of explantation; indeed, in many cases they were more widespread than are their differentiated progeny in normal gut of the same age. This finding indicates that conditions in grafts must differ from those that operate in the intact embryo. Also it may explain the occurrence of ectopic gut or pancreatic endocrine cells in tumours of the digestive tract.

Animals↗
PubMed1980

Endocrine cell carcinoma of the uterine cervix.

We present an endocrine cell carcinoma of the uterine cervix in a 21-year-old woman which we studied by histochemical, immunocytochemical, and ultrastructural methods. The tumor had a histologic appearance similar to an oat cell carcinoma, and carcinoma in situ changes were found in the adjacent cervical surface epithelium. Histochemistry and electron microscopy revealed argyrophil cells containing small round secretory granules; more rarely argentaffin (enterochromaffin) cells were seen with dense, elongated and pleomorphic granules and numerous undifferentiated cells with few and small granules. Our findings indicate that the different types of endocrine tumor cells have the same stem cell origin and necessitate the revision of some of the concepts of the embryogenesis of the APUD cells and their tumors. We emphasize that all undifferentiated or poorly differentiated carcinomas of the uterine cervix should be examined histochemically and ultrastructurally, particularly since their correct classification has prognostic and therapeutic implications.

Adult↗
PubMed2002

An immunohistochemical study of pancreatic endocrine cells in SKH-1 hairless mice.

The regional distribution and frequency of the pancreatic endocrine cells in the SKH-1 hairless mouse were studied by an immunohistochemical (peroxidase anti-peroxidase; PAP) method using four types of specific antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (PP). The pancreas of mice were divided into three portions; pancreatic islets, exocrine and pancreatic ducts. The pancreatic islets were further subdivided into three regions (central, mantle and peripheral region) according to their located types of immunoreactive cells. In the pancreatic islet portions, insulin-immunoreactive cells were located in the central and mantle regions with 84.60 +/- 7.65 and 33.00 +/- 12.45/100 cells frequencies, respectively, but most of somatostatin-, glucagon- and PP-immunoreactive cells were detected in the mantle and peripheral regions. In the mantle region, somatostatin-, glucagon- and PP-immunoreactive cells were demonstrated with 28.70 +/- 9.91, 52.00 +/- 14.05 and 2.60 +/- 1.51/100 cells frequencies, respectively, and showed 6.20 +/- 2.86, 15.30 +/- 5.31 and 21.50 +/- 10.28/100 cells frequencies, respectively in peripheral regions. However, glucagon-immunoreactive cells were also demonstrated in the central regions with 4.00 +/- 2.83/100 cells frequency. In the exocrine portions, insulin-, glucagon-, somatostatin- and PP-immunoreactive cells were demonstrated in the SKH-1 mouse with 0.90 +/- 0.74, 0.80 +/- 0.79,4.90 +/- 3.54 and 2.70 +/- 1.34/100 cells frequencies, respectively. In the pancreatic duct portions, insulin-, glucagon- and somatostatin-immunoreactive cells were demonstrated in the subepithelial connective tissues and showed islet-like appearances with 30.30 +/- 14.67, 2.70 +/- 3.13 and 5.90 +/- 4.23/100 cells frequencies, respectively. However, no PP-immunoreactive cells were demonstrated in these regions. In conclusion, some peculiar distributional patterns of pancreatic endocrine cells were found in the SKH-1 hairless mouse.

Animals↗
PubMed1983

Argyrophil endocrine cells with ACTH and HCG immunoreactivity in a carcinoma of the breast.

A middle-aged woman without any symptoms of ectopic hormone production underwent a right-sided mastectomy for infiltrating ductal carcinoma. She later developed axillary lymph node metastases which were somewhat carcinoid-like. This prompted further investigation, when scattered argyrophilic endocrine cells were found in both the primary tumour and its metastases. The endocrine cells reacted immunocytochemically with antisera against ACTH and HCG. Despite the endocrine activity of the tumour, it was still regarded as a ductal carcinoma since the endocrine cells constituted the minority cell population. The present study indicates strongly that ectopic hormone production in association with carcinoma of the breast is a result of hormone synthesis and release by the tumour cells.

Adrenocorticotropic Hormone↗
PubMed1989

Multicentric gastric carcinoids complicating pernicious anemia. Origin from the metaplastic endocrine cell population.

We report three cases of multicentric carcinoid tumors of the stomach in patients with long-standing pernicious anemia and severe atrophic gastritis (type A). The tumor nodules arose in nonantral gastric mucosa showing marked intestinal metaplasia. Diffuse endocrine cell hyperplasia was present in both fundus and antrum. Antral G-cell hyperplasia was observed. A widely accepted pathogenesis of this syndrome suggests that the proliferating cell type is the argyrophilic, enterochromaffinlike cell native to the gastric body and fundus. Our findings conflict with this view, in that focal argentaffin staining was also present within tumor cells, as well as immunoreactivity for serotonin and substance P (more characteristic of small-intestinal enterochromaffin or Kulchitsky's cells and small-intestinal carcinoids). Findings in these cases at least suggest an alternative possibility: the tumors may derive from small-intestinal-type metaplastic endocrine cells within the atrophic mucosa, rather than the hypertrophic native endocrine cell population.

Adenocarcinoma↗
PubMed1986

FMRFamide- and pancreatic polypeptide-like immunoreactivity of endocrine cells in the midgut of a mosquito.

Immunocytochemical surveys of midguts from female mosquitoes, Aedes aegypti, reveal that half of the estimated 500 endocrine cells in a midgut contain a substance recognized by antisera to bovine pancreatic polypeptide and a molluscan peptide, FMRFamide (phenylalanine-methionine-arginine-phenylalanine-amide). With light microscopy the cells resemble an endocrine type because of their basal position in the epithelium, conical shape, and, in some instances, apical extensions to the lumen. At the ultrastructural level, the immunoreactive substance is contained specifically within the secretory granules of such cells. Immunoreactive cells are distributed exclusively in the midgut region where blood is stored, and ingestion of vertebrate blood reduces the number of such cells and the intensity of reaction in others. These two facts suggest that a blood meal stimulates release of the immunoreactive substance from the cells. Since the immunocytochemical localization is supplemented by a demonstrated secretory response, the cells are considered to be peptidergic endocrine cells.

Aedes↗
PubMed1980

The endocrine cells of the pyloric glands of adult ox.

As part of a project to identify the endocrine cells ("EC" and "APUD" series) of the gastroenteric apparatus of ruminants, the ultrastructure of the mucosa of the pyloric glands of adult ox was studied morphologically and cytochemically, in parallel with a light microscope histochemical analysis. The results show that: the "EC" cells (producing 5-HT) are recognizable by their secretory granules which are heavily osmiophilic, argentaffin ("Masson") and argyrophilic ("Grimelius"). A further distinction is possible on the basis of their morphological features: the ""EC" cells of the gastric type (which belong to the "ECn" group) contain granules fairly homogeneous in shape and size, while the "EC" cells of the intestinal type (or "EC1") show granules which are more pleiomorphic and variable in size. Of particular interest is the presence in some cells of granules typical of the "EC" cells of the intestinal type, in the vicinity of a few others, which appear quite similar to those of the adjoining exocrine cells; the "G" cells (gastrin producing) contain medium sized granules, which are unreactive to "Masson" and poorly argyrophilic. Their morphology is rather diverse; some of them (these are the "typical" cells) have a granular and weakly electron dense content, others (which we consider "atypical") show a homogeneous and heavily osmiophilic core, with an eccentrical empty area. Also present are granules whose appearance is intermediate and empty vesicles; the "D cells" (somatostatin producting) show round, medium sized granules which have a granular, moderately osmiophilic core, tightly encircled by the membrane. These granules are unreactive to "Masson" and to "Grimelius"; the "D1" cells (whose function is yet unclear) contain small, round granules whose core is variously but discretely electron dense and not always homogeneous; they are unreactive to "Masson" and fairly argyrophilic. These granules may be numerous and packed, or scarce; in this latter instance the few granules are intermingled with variously running tufts of parallel filaments, thus resembling the "P" cells, whose function is still undefined. These data show therefore that the types of endocrine cells we have identified in the pyloric glands of adult ox correspond to those described in other mammals; "X" and "F" or "PP" cell appear to be lacking.

APUD Cells↗