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PubMed1988

Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons.

Insulin appears in the developing mouse pancreas at embryonic day 12 (e12). Transgenic mice harboring three distinct hybrid genes utilizing insulin gene regulatory information first express the transgene product two days earlier, at e10, in a few cells of the pancreatic bud. Throughout development and postnatal life, all of the insulin-producing (beta) cells coexpress the hybrid insulin gene. In addition, islet cells containing glucagon, somatostatin, pancreatic polypeptide, and the neuronal enzyme tyrosine hydroxylase coexpress the transgene when they first arise. Similarly, coexpression of these normally distinct islet cell markers occurs during differentiation of the four endocrine cell types. The transgene product also appears transiently during embryogenesis in cells of the neural tube and in neural crest. The results suggest a common precursor for the endocrine cells of the pancreas. Moreover, they imply a relationship between neural and pancreatic endocrine tissue.

Animals↗

PubMed1991

An immunohistochemical study of the gastro-entero-pancreatic endocrine cells in the alimentary tract of the Korean tree squirrel, Sciurus vulgaris corea.

The regional distribution and relative frequencies of gastrointestinal endocrine cells were studied immunohistochemically in the gastrointestinal mucosa of Korean tree squirrels. Seven kinds of endocrine cells were identified in this study. Although a large number of 5-hydroxytryptamine-immunoreactive cells were seen throughout the gastrointestinal tract, they were most predominant in the duodenum. A moderate number of glucagon-immunoreactive cells which were restricted to the cardia and fundus of the stomach was also observed. Bovine chromogranin-immunoreactive cells were numerous in the cardia and pylorus of the stomach, found in moderate numbers in the fundus, duodenum and large intestine, but rare in the jejunum. Porcine chromogranin-immunoreactive cells were found in moderate numbers in the stomach but were rare in the duodenum. Gastrin/cholecystokinin-immunoreactive cells were abundant in the pyloric gland region but scarce in the duodenum. Bovine pancreatic polypeptide-immunoreactive cells were observed to be rare and found only in the pyloric gland region. Somatostatin-immunoreactive cells were distributed moderately in the stomach but were few in number in the intestine. No insulin-immunoreactive cells were found in the gastrointestinal tract of Korean tree squirrels. These results suggest that although the Korean tree squirrel is a herbivorous rodent, the distribution pattern of its gastro-entero-endocrine cells is rather similar to that reported for omnivorous animals.

Animals↗

PubMed1983

Cellular kinetics of gastrointestinal mucosa, with special reference to gut endocrine cells.

After 3H-thymidine autoradiography was introduced to the study of cellular kinetics, the epithelial cells of the gastrointestinal mucosa have been examined extensively with regard to their kinetic behavior. After reviewing the knowledge on the kinetics of different epithelial cells in the stomach and small and large intestine, this article concentrates on the origin, differentiation and turnover of gut endocrine cells which have been under much controversy. Autoradiographic and other investigations of EC cells support the view that these cells are not neuroectodermal in origin, but differentiate from an immature type of gut epithelial cells. We investigated the kinetics of the antral G cells in the hamster, G cells and S cells in the rat duodenum by the combined utilization of 3H-thymidine autoradiography with immunohistochemistry, and confirmed that these cells are derived from the same precursor cells as the other mucosal cells of the gastrointestinal tract. The half-life of the antral G cells was estimated at 10-15 days, while the turnover time of the G cells and S cells in the duodenum were calculated at 3-4 days and 2 days, respectively. These data also support the belief that gut endocrine cells originate from the endoderm. Histopathological alterations such as antral gastritis and intestinal metaplasia, as well as vagal denervation, were shown to influence the population of the antral G cells in man and the hamster. This supports the view that intrinsic and extrinsic stimuli might alter the kinetics of gut endocrine cells.

Animals↗

PubMed1986

Gut endocrine cells in rat stomach carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine.

Gut endocrine cells in a total of 18 gastric adenocarcinomas in inbred Wistar rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and gastrin or serotonin, were examined histologically, ultrastructurally, and immunohistochemically for gastrin, somatostatin, calcitonin, glicentin, and serotonin. A large number of argyrophil cells were observed in 17 tumors (94.4%) and 14 tumors (77.8%) had argentaffin cells. Immunohistochemically, C-terminal fragment of gastrin (G17) immunoreactivity was observed in 15 (82.2%) out of the 18 tumors, but 3 G17-positive tumors had no G 34 immunoreactive cells in rats treated with MNNG plus gastrin. Serotonin immunoreactivity was detected in 14 tumors (77.8%). Somatostatin immunoreactivity was detected in 7 of the 11 tumors (63.6%) in rats treated with MNNG plus gastrin whereas no tumor in rats treated with MNNG plus serotonin had somatostatin, the difference of the incidence being significant (P less than 0.05). One endocrine cell carcinoma which consisted mainly of serotonin-producing cells was observed in a rat treated with MNNG plus serotonin. Calcitonin and glicentin immunoreactivity was not demonstrated in any tumors. Ultrastructurally, three types of endocrine granule were found in the tumor cells. These data suggest that hormonal environment in stomach carcinogenesis may influence the expression of endocrine cells within the tumors.

Adenocarcinoma↗

PubMed1982

Regeneration of endocrine cells in the stomach.

A mucosal defect was produced by cryosurgery in the antral and the fundic wall of the rat stomach, and regeneration of gastric endocrine cells was studied 50, 100 and 200 days after operation. Fifty days after the operation, the mucosal defect was completely covered with regenerated epithelium. The regenerated mucosa both in the antral and in the fundic region consisted of mucinous glandular structures. The regenerated mucosa in the corpus remained pseudopyloric in type even 200 days after operation. Regardless of the time after operation, regeneration of endocrine cells was always observed. We could identify G cells and EC cells in the regenerated mucosa of the antrum, and EC cells, A cells and AL cells in the regenerated mucosa of the corpus, respectively. By electron microscopy, endocrine-exocrine cells were frequently encountered. These cells had two different types of intra-cytoplasmic granules; one was an endocrine-specific, small electron-dense granule, and the other a large, lucent mucin droplet-like granule. These findings indicate that the endocrine cells of the stomach are formed from endodermal precursor cells.

Animals↗

PubMed2000

Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3.

Hepatocyte nuclear factor 6 (HNF-6) is the prototype of a new class of cut homeodomain transcription factors. During mouse development, HNF-6 is expressed in the epithelial cells that are precursors of the exocrine and endocrine pancreatic cells. We have investigated the role of HNF-6 in pancreas differentiation by inactivating its gene in the mouse. In hnf6(-/-) embryos, the exocrine pancreas appeared to be normal but endocrine cell differentiation was impaired. The expression of neurogenin 3 (Ngn-3), a transcription factor that is essential for determination of endocrine cell precursors, was almost abolished. Consistent with this, we demonstrated that HNF-6 binds to and stimulates the ngn3 gene promoter. At birth, only a few endocrine cells were found and the islets of Langerhans were missing. Later, the number of endocrine cells increased and islets appeared. However, the architecture of the islets was perturbed, and their beta cells were deficient in glucose transporter 2 expression. Adult hnf6(-/-) mice were diabetic. Taken together, our data demonstrate that HNF-6 controls pancreatic endocrine differentiation at the precursor stage and identify HNF-6 as the first positive regulator of the proendocrine gene ngn3 in the pancreas. They also suggest that HNF-6 is a candidate gene for diabetes mellitus in humans.

Animals↗

PubMed1999

Abnormal colonic endocrine cells in patients with chronic idiopathic slow-transit constipation.

BACKGROUND: The aim of the present study was to investigate the colonic endocrine cells in patients with slow-transit constipation, to ascertain the presence of a possible abnormality. METHODS: Ten patients with chronic slow-transit constipation were investigated. As controls, macroscopically and histologically normal tissues from the colon of 12 patients were examined. These patients had polyps, prolapsis, chronic diverticulitis, volvulus, and haemorrhoids. The endocrine cells were stained by immunocytochemistry and quantified by computerized image analysis. RESULTS: There were significantly fewer enteroglucagon- and serotonin-immunoreactive cells in patients with chronic slow-transit constipation. There was no statistically significant difference between patients and controls with regard to the number of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and somatostatin-immunoreactive cells. The cell secretory indexes (CSI) of enteroglucagon- and somatostatin-immunoreactive cells were significantly decreased. There was no statistically significant difference in the CSI between the patients and controls with regard to PYY-, PP-, and serotonin-immunoreactive cells. CONCLUSION: The changes in colonic endocrine cells in patients with slow-transit constipation may be one cause of the decreased motility in the colon and consequent development of constipation.

Adult↗

PubMed1999

Differences in the ways sympathetic neurons and endocrine cells process, store, and secrete exogenous neuropeptides and peptide-processing enzymes.

Most neurons store peptides in large dense core vesicles (LDCVs) and release the neuropeptides in a regulated manner. Although LDCVs have been studied in endocrine cells, less is known about these storage organelles in neurons. In this study we use the endogenous peptide NPY (neuropeptide Y) and the endogenous peptide-processing enzyme PAM (peptidylglycine alpha-amidating monooxygenase) as tools to study the peptidergic system in cultured neurons from the superior cervical ganglion (SCG). Once mature, SCG neurons devote as much of their biosynthetic capabilities to neurotransmitter production as endocrine cells devote to hormone production. Unlike pituitary and atrium, SCG neurons cleave almost all of the bifunctional PAM protein they produce into soluble monofunctional enzymes. Very little PAM or NPY is secreted under basal conditions, and the addition of secretagogue dramatically stimulates the secretion of PAM and NPY to a similar extent. Although endocrine cells typically package "foreign" secretory products together with endogenous products, pro-opiomelanocortin- and PAM-derived products encoded by adenovirus in large part were excluded from the LDCVs of SCG neurons. When expressed in corticotrope tumor cells and primary anterior pituitary cultures, the same virally encoded products were metabolized normally. The differences that were observed could reflect differences in the properties of neuronal and endocrine peptidergic systems or differences in the ability of neurons and endocrine cells to express viral transcripts.

Adenoviridae↗

PubMed1988

Immunocytochemical and ultrastructural characterization of coexistence of pancreatic polypeptide and glucagon-like immunoreactivity in the pancreatic endocrine cells of Sparus auratus L. (Teleostei).

Coexistence of pancreatic polypeptide (PP)- and glucagon-like immunoreactivity was demonstrated in the pancreatic endocrine cells of the teleost fish Sparus auratus. An immunofluorescence double-staining method revealed coexistence of glucagon- and PP-like immunoreactivity in endocrine cells of small and intermediate islets. In contrast to small islets, the intermediate ones also contained a variable number of glucagon-immunoreactive cells next to cells having both immunoreactivities. Coexistence of both immunoreactivities could not be observed in endocrine cells of the principal islet, whereas many cells containing glucagon and a few cells containing PP immunoreactivity were found. By an immunogold double-staining method the precise ultrastructural location of each immunoreactivity could be demonstrated. Again, cells containing glucagon- and/or PP-like immunoreactivity were found. Although, only two different types of granules were observed, four distinct cell types could be distinguished. Based on this granule morphology two cell types showing coexistence were found: one cell type, only present in the small islets, showing a different distribution of glucagon and PP immunoreactivity within the granules (predominantly in the center and periphery, respectively) and another cell type with larger granule cores, present in small as well as intermediate islets, having a mixed distribution of both immunoreactivities.

Animals↗

PubMed1984

Endocrine cells in intestinal metaplasia of the stomach.

In this study we have investigated the mucin profile and the endocrine cell population in gastric endoscopic biopsies from 22 patients affected by chronic gastritis and intestinal metaplasia and in five surgical specimens of stomachs removed because of intestinal-type carcinoma (4) or peptic ulcer (1). High iron diamine-Alcian blue (HID-Ab) staining and peptide immunocytochemistry (peroxidase anti-peroxidase technique) were used. Forty-one foci of intestinal metaplasia were detected, 15 produced sulphomucins and 26 sialomucins. Of the endocrine cells investigated, gastrin and somatostatin cells were the most frequently observed, while cholecystokinin, glucose-dependent insulinotropic peptide-, secretin- and enteroglucagon-containing cells were also found in the metaplastic areas, but less frequently. No significant correlation was found between the type of mucin and the types of endocrine cells present, the latter usually resembling those normally found in the small intestine. On the basis of these results we conclude that intestinal metaplasia involves mucin- and peptide-producing cells of the stomach in a variable manner, with no correlation between the two.

Adult↗

PubMed1986

Ultrastructural localization of serotonin and polypeptide YY (PYY) in endocrine cells of the human rectum.

This study was performed with the aim of ultrastructurally localizing serotonin and polypeptide YY (PYY) in the endocrine cells of the human rectum. Existing basic methods for immunolocalization of antigenic sites in ultrathin sections were tested and modified to allow reproducible results with distinct localization of marker (colloidal gold probes coupled either to IgG or protein A). Probes signifying presence of serotonin were distinctly localized over all heteromorphous granules in argentaffin cells and, in addition, over some of the more monomorphous, rounded granules in a second cell type whose granules all were covered by probes showing localization of the PYY antigen. The results suggest that serotonin in endocrine cells of the gut is not confined to the enterochromaffin type but may also be present in trace amounts in non-enterochromaffin endocrine cells storing peptide hormones. Since probes marking sites of PYY were deposited over some heteromorphous granules in enterochromaffin cells, the evidence obtained also suggests that PYY may occur in low concentration in these cells. The distribution of probes in the sections indicated that antigenic sites were confined to granules in the cells.

Cell Nucleus↗

PubMed1987

Endocrine cells of the gastric mucosa of Rana temporaria L.

The endocrine cells of the gastric mucosa of Rana temporaria have been studied according to the ultrastructure, the staining properties of the granules with Masson Fontana's and Grimelius' silver methods, silver impregnation of Davenport on deplasticised semithin sections and immunocytochemical techniques. Seven different types of endocrine cells have been described. Six were regarded as belonging to known types: G, A, EC, ECL, D and P cells. One type was considered as unclassifiable.

Animals↗

PubMed2002

Granule changes of human and murine endocrine cells in the gastrointestinal epithelia are characteristic of piecemeal degranulation.

Piecemeal degranulation is a unique pattern of cell secretion that consists of a slow release of granule contents from cytoplasmic secretory granules, which leaves empty chambers that do not fuse with each other or with the plasma membrane. To our knowledge, no cell types other than mast cells, basophils, and eosinophils have been reported in the literature to show morphological features of piecemeal degranulation. In the present study we provide evidence for ultrastructural morphologies characteristic of piecemeal degranulation in entero-endocrine cells of the human and murine gastrointestinal epithelia. Human biopsy samples were taken from the mucosa of the distal duodenum, proximal jejunum, and colon in 10 patients undergoing endoscopic examination for malabsorption, diarrhea, and/or abdominal pain. Murine gastrointestinal samples were obtained from 10 adult C57 mice. All specimens were prepared for transmission electron microscopy (TEM) according to standard protocols. Results showed that different types of gastrointestinal entero-endocrine cells, in both humans and mice, were recognizable with ultrastructural features diagnostic for piecemeal degranulation, including specific granule and cytoplasmic changes. In the granules, the content was found to be loosely packed or diminished. Notably, altered granules did not fuse with each other or with the plasma membrane, and were characteristically intermingled with normal, resting granules. At times, the release events transformed the granules into enlarged, empty containers. Numerous entero-endocrine cells presented a rich supply of membrane-bound vesicles (50-200 nm in diameter) that were free in the cytoplasm or attached to granules. This finding of piecemeal degranulation in gastrointestinal entero-endocrine cells suggests that such a secretory model might be a general degranulation pattern in cells involved in paracrine-endocrine secretion.

Adolescent↗

PubMed1988

Can proventricular mesenchyme promote differentiation of endocrine cells in gizzard endoderm?

Previous findings prompted the suggestion that avian proventricular mesenchyme might induce differentiation of endocrine cells with gastrin-releasing peptide (GRP)-like immunoreactivity in endoderm from an organ which, at hatching, is deficient in such cells. Therefore gizzard endoderm and proventricular mesenchyme from chick embryos of 5 days' incubation were combined and grown as chorio-allantoic grafts. Controls comprised re-associated endoderm and mesenchyme of the gizzard and of the proventriculus. In the experimental grafts, as in proventricular controls, immunocytochemistry revealed not only GRP cells, but also the other endocrine cell types characteristic of proventriculus. All these cell types were either absent or very rare in gizzard controls.

Animals↗

PubMed1995

Endocrine cells of transitional mucosa adjacent to colonic adenocarcinoma.

Transitional mucosa (TM) is used to describe mucosa adjacent to colonic adenocarcinoma with characteristic morphological and histochemical features. There is currently much debate about its aetiology. Some suspect it to be premalignant; others view it as a reactive change. Studies have looked at the morphology of TM and the type of mucins secreted by goblet cells within TM. Little work has been done on the third group of cells present in colonic mucosa; the enteroendocrine cells. These cells have many functions concerned predominantly with modulating the local environment. They are thought to be able to influence growth and metabolism. There is growing evidence in animal studies which suggest that hormones present within endocrine cells of colonic mucosa can influence colonic tumour growth rates. In this study endocrine cells stained with histochemical and immunocytochemical techniques were examined under the light microscope. Serotonin immunoreactive cells, the predominating endocrine cells of colonic epithelium, were present in greater numbers within the TM. Their increase was proportional to the increase in height of the mucosa of the TM. The increase was also proportional to the increase in epithelial cell numbers within the mucosa. This suggests that they proliferate together with the other epithelial cells of TM. In conclusion, serotonin containing cells appear to be an integral component of TM.

Adenocarcinoma↗

PubMed1984

Neuron specific enolase: a marker for the early development of nerves and endocrine cells in the human lung.

Neuron specific enolase (NSE), an isoenzyme of the glycolytic enzyme enolase, has been established by immunocytochemical means as a marker of morphological and functional maturation in central neurons and appears late in development. However, little is known about the presence of NSE in developing peripheral neurons and endocrine cells and its relationship to the development of classical neurotransmitters and peptides. We therefore investigated the appearance of NSE immunoreactivity in nerves and mucosal endocrine cells of the human respiratory tract in foetal, neonatal and adult life. NSE was found to be present in neuroblasts, nerve fibres and endocrine cells from the earliest period of gestation examined (8 weeks), before the appearance of acetylcholinesterase activity (10-12 weeks), dopamine-beta-hydroxylase (20 weeks), vasoactive intestinal polypeptide (20 weeks) or calcitonin (20 weeks). Bombesin-like immunoreactivity was found in a small proportion of mucosal endocrine cells as early as eight weeks in the foetal respiratory tract. These findings indicate that unlike central neurons and their processes, peripheral neurons of the lung contain NSE immunoreactivity well before full maturation and establishment of synaptic contact with end organs.

Endocrine Glands↗

PubMed1993

An immunohistochemical study on the gastrointestinal endocrine cells of three honeyeaters: singing honeyeater (Meliphaga virescens), spiny-cheeked honeyeater (Acanthogenys rufogularis) and brown honeyeater (Lichmera indistincta).

The gastrointestinal endocrine cells of the singing honeyeater (Meliphaga virescens), spiny-cheeked honeyeater (Acanthogenys rufogularis) and brown honeyeater (Lichmera indistincta) were studied immunohistochemically with special reference to their degree of dependency upon nectar. The nine types of immunoreactive endocrine cells were detected in their gastrointestinal mucosa. Coexistence of motilin and serotonin in the same cells was confirmed in the pyloric region. In the duodenum and jejunum, a few peptide tyrosin tyrosin (PYY)-immunoreactive cells were detected. The clear difference in the distribution and frequency of the gastrointestinal endocrine cells among three types of honeyeaters, which differ in the degree of dependency upon the nectar, could not be confirmed. However, some differences were found that serotonin-, somatostatin- and gastrin-releasing peptide (GRP)-immunoreactive cells in the gizzard, gastrin-immunoreactive cells in the duodenum and jejunum, enteroglucagon-immunoreactive cells in the caeca and in the colon, and pancreatic glucagon-immunoreactive cells in the ileum of brown honeyeaters were more numerous (p < 0.05) than other two species.

Animals↗

PubMed1990

An ultrastructural study on gastric endocrine cells in the stomach gland patch of the koala Phascolarctos cinereus.

The endocrine cells in the stomach gland patch of the koala (Phascolarctos cinereus) were studied ultrastructurally. They were classified into 3 types based on the ultrastructural profiles of their endocrine granules and tentatively categorized as type I, II, and III endocrine cells. Type I cells contained round granules that were for the most part larger than those observed in the other 2 cell types. The granules ranged from moderate to relatively high in electron density. Type II cells were angular in shape and characterized by the presence of granules that were polymorphous in profile. Contents of the endocrine granules in type II cells also showed a range of high to moderate electron density. Type III cells were oval or pyramidal in shape. They contained highly polymorphous granules that were round, oval, dumbbell-like or comma in shape and characterized by the presence of a clear space or halo separating the high to low electron-dense core from the limiting membrane of granules. Type III cells were observed most often whereas type I and II cells were a less frequent observation.

Animals↗