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At least 145 records · Page 8Linked to original sources
PubMed1990

Glucagon-like immunoreactivity in hypothalamic neurons of the rat.

Antisera specific for three different regions of pancreatic proglucagon were used to examine the distribution of such immunoreactivity in rat hypothalamus. Neurons in the supraoptic and paraventricular nuclei were immunoreactive with an antiserum against glucagon, but not with antisera directed towards the aminoterminal region of proglucagon (glicentin) or the glucagon-like peptide I sequence in the carboxyl-terminal region of proglucagon. These findings confirm a previous report of glucagon-like immunoreactivity in the supraoptic and paraventricular nuclei, but indicate that, while this material is immunochemically related to glucagon, it is not derived from a proglucagon-like precursor.

Animals↗
PubMed1994

Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study.

The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Electron microscopic studies of endocrine hyperplasia in duodenal adenomas in familial adenomatous polyposis.

Electron microscopical studies on endocrine cell hyperplasia of duodenal adenomas from five patients with familial adenomatous polyposis were performed. All the endocrine cell types normally found in the duodenal mucosa were identified. A constant feature was proliferation of duodenal-enterochromaffin cells but an increase in the number of all other endocrine cell types apart from pyloric-gastrin cells and somatostatin cells, was also observed. Certain types of intestinal endocrine cells (the intestinal enterochromaffin cell and the glicentin cell) are rare cells in the normal duodenal mucosa. The finding of these cells may indicate increased biological aggressivity.

Adenoma↗
PubMed1984

Distribution of Leu 7 (HNK-1) antigen in human digestive organs: an immunohistochemical study with monoclonal antibody.

Leu 7 immunoreactivity was demonstrated with the indirect peroxidase-labelled antibody method on frozen and paraffin-embedded tissue sections of human digestive organs. Anti-Leu 7 monoclonal antibody, which allegedly detects mononuclear cells with natural killer or killer activity, recognized lymphoid cells among intestinal epithelial cells and in the germinal centres of solitary lymphoid follicles of small and large intestine, and a few in gallbladder, liver and the lamina propria of the intestine. In addition, peripheral nerve fibres, endocrine cells in the gut and pancreas and carcinoid and islet cell tumours were also positively stained. At the ultrastructural level, Leu 7 antigen was localized on the plasma membrane of granulated lymphoid cells in the gut mucosa and on the secretory granules of intestinal endocrine cells. In normal pancreas, Leu 7 immunoreactivity was demonstrated in most cells containing pancreatic polypeptide and in many cells containing somatostatin or glicentin. Insulin-containing cells, however, lacked Leu 7 immunoreactant. These findings were obtained in both frozen sections and paraffin-embedded sections. The possible cross-reactivities of monoclonal antibodies are discussed as they raise an important caveat in immunohistochemical studies using these antibodies.

Adult↗
PubMed1997

Immunohistochemical localization of acidic fibroblast growth factor in normal human enterochromaffin cells and related gastrointestinal tumours.

Acidic fibroblast growth factor (aFGF) is a member of the structurally related heparin-binding growth factor family. The best studied members of this family are aFGF and basic FGF (bFGF), which are potent mitogens and differentiation factors for mesoderm-derived cells, including fibroblasts. This study was designed to verify the immunohistochemical expression of aFGF in normal human endocrine cells of the gut and in related endocrine tumours. We examined normal gastrointestinal mucosa from seven different subjects and 41 gut endocrine tumours from different sites, including stomach, duodenum, and small and large intestine, using an aFGF polyclonal antibody with no cross-reactivity for bFGF. We localized aFGF in a fraction of serotonin-producing enterochromaffin (EC) cells of the normal gut, while it was absent in gastrin (G), CCK, secretion (S), somatostatin (D) and glicentin (L) cells. aFGF immunoreactivity was also expressed in serotonin producing EC cell tumours, but not in other functional types of gut endocrine neoplasms investigated, including gastric ECL cell, duodenal somatostatin and gastrin cell, and rectal L cell tumours. A positive correlation was found between expression of aFGF and the amount of tumour fibrous stroma, suggesting that aFGF may be involved in proliferation and activity of stromal fibroblasts.

Adolescent↗
PubMed1991

Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy.

Postprandial glucagon-like peptide-1 (GLP-1), pancreatic glucagon, and insulin were measured in 27 tumor-free patients 43 months (median) after total gastrectomy and in four controls using a 99technetium-labeled 100-g carbohydrate solid test meal. Emptying of the gastric substitute was measured by scintigraphy. Fourteen patients suffered from early dumping symptoms, and five of them also reported symptoms suggestive of reactive hypoglycemia (late dumping). The median emptying half-time (T1/2) of the gastric substitute was 480 sec. Sigstad's dumping score was 8.5 +/- 1.6 (mean +/- SE) in patients with rapid emptying (T1/2 less than 480 sec), and 3.0 +/- 1.5 in patients with slow emptying of the gastric substitute (P = 0.02). The peak postprandial concentration of GLP-1 was 44 +/- 20 pmol/liter in controls, 172 +/- 50 in patients without reactive hypoglycemia, and 502 +/- 116 in patients whose glucose fell below 3.8 mmol/liter during the second postprandial hour. Plasma GLP-1 concentrations peaked at 15 min, and insulin concentrations at 30 min after the end of the meal. A close correlation between integrated GLP-1 responses and integrated insulin responses (r = 0.68) was observed. Multiple regression revealed that three factors were significantly associated with the integrated glucose concentrations during the second hour (60-120 min): Early (first 30 min) integrated GLP-1 (inverse correlation; P = 0.006), age (P = 0.006), and early integrated pancreatic glucagon (P = 0.005). There was a close (inverse) relationship of T1/2 with early integrated GLP-1 and pancreatic glucagon, but not with insulin. Gel filtration of pooled postprandial plasma of gastrectomized individuals revealed that all glucagon-like immunoreactivity eluted at Kd 0.30 (Kd, coefficient of distribution), the elution position of glicentin. Almost all of the GLP-1 like immunoreactivity eluted at Kd 0.60, the elution position of gut GLP-1. The authors contend that GLP-1-induced insulin release and inhibition of pancreatic glucagon both contribute to the reactive hypoglycemia encountered in some patients following gastric surgery. Rapid emptying seems to be one causative factor for the exaggerated GLP-1 release in these subjects.

Blood Glucose↗
PubMed1987

Endocrine cells in the human colorectal mucosa: immunocytochemical observations on patients with prolapse or internal procidentia of the rectum.

We have examined the occurrence and distribution of endocrine cells storing serotonin and the regulatory peptides somatostatin, glicentin, peptide YY in rectal mucosa on 16 patients with prolapse or intussusception of the rectum. There were no significant differences compared with normal rectal mucosa. Our results do not support the assumption that these endocrine cells of the rectum are involved in the pathophysiology of rectal prolapse.

APUD Cells↗
PubMed1988

The use of plasma desorption time-of-flight mass spectrometry to screen for products of prohormone processing in crude tissue extracts.

Californium-252 plasma desorption mass spectrometry (252Cf PDMS) of a crude, desalted, extract of piscine endocrine pancreas provided mass information for the major biologically active peptide hormones present in this tissue. An extraction procedure compatible with 252Cf PDMS analysis was developed. In extracts of catfish pancreas, strong molecular ions were identified in the positive mode for somatostatin-14 (1638 amu), O-glycosylated somatostatin-22 (2944 amu), glucagon (3512 amu), glucagon-like peptide (3785 amu), insulin (ca. 5550 amu), and other prohormone-derived peptides. Both protonated species and sodium adducts were apparent in the mass spectrum. A number of other molecular ions were observed including somatostatin-26, 1-10 (1014 amu) and the entire portion of prosomatostatin-22 remaining after removal of somatostatin-22 (6465 amu). The data obtained by this method also resulted in the identification of the third major product of proglucagon processing in catfish pancreas, glicentin-related polypeptide. Subtractive Edman degradation analyzed by 252Cf PDMS was also used to confirm a mass assignment.

Amino Acid Sequence↗
PubMed1989

Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells.

In this immunocytochemical study, we have analyzed the developmental profile and phenotypic expression of the endocrine cell antigens chromogranin, 5-hydroxytryptamine, gastrin/cholecystokinin, cholecystokinin (9-20), somatostatin, somatostatin 28 (1-14), somatostatin cryptic peptide, glucagon, glucagonlike peptides 1 and 2, glicentin, peptide YY, glucose-dependent insulinotropic peptide, secretin, neurotensin, and substance P in human fetal stomach and intestine. All currently identifiable endocrine cell types were detected by 10 wk of gestation. Immunostaining for the endocrine cell marker chromogranin revealed abundant endocrine cells in the earliest specimens (8 wk of gestation) with a relatively higher frequency in both proximal duodenum and distal colon/rectum compared with other areas. Quantification of endocrine cells showed an increase with age that was roughly parallel to the growth of the gut as a whole. These studies show that the diversity of the endocrine component of the gut appears to be established by 10 wk of gestation and that gut activity is preceded by the development of a fully differentiated endocrine component, which may subserve or even initiate the onset of functional maturity.

Antibodies, Monoclonal↗
PubMed1984

Immunocytochemical evidence for the occurrence of insulin in the frontal ganglion of a Lepidopteran insect, the tobacco hornworm moth, Manduca sexta L.

The frontal ganglion of the adult forms of the tobacco hornworm, Manduca sexta, was investigated immunocytochemically for the occurrence of the gastro-entero-pancreatic (GEP) neurohormonal peptides, namely insulin, nerve growth factor, epidermal growth factor, insulin C-peptide, somatostatin, glucagon, glicentin, pancreatic polypeptide (PP), polypeptide YY (PYY), secretin, vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP), gastrin, cholecystokinin (CCK), enkephalin, alpha- and beta-endorphins, substance P, neurotensin, bombesin, motilin, ACTH, serotonin, and calcitonin. Among all the antisera tested, positive immunostaining was obtained with anti-insulin B-chain serum only. The insulin B-chain immunoreactivity was localized in 4-6 large (30-40 microns) neurons, in the neuropile, and in the recurrent nerve. It is speculated that the insulin-like immunoreactive material may be transported to the neurohaemal organ (corpora cardiaca) through the nervi cardiaco-somatogastrici.

Animals↗
PubMed1990

Immunohistochemical and ultrastructural studies of twelve argentaffin and six argyrophil carcinoids of the appendix vermiformis.

Endocrine cell types in 12 argentaffin and six argyrophil carcinoids and in nonneoplastic epithelia of the appendix vermiformis were investigated histochemically, immunohistochemically, and ultrastructurally. The nonneoplastic epithelia contained serotonin (Ser), peptide YY (PYY), glicentin (Gli), neurotensin (Neu), and somatostatin (So) cells in decreasing frequency. Out of 30 nonneoplastic Ser cells examined ultrastructurally, 28 cells were EC1 cells and two were non-EC cells. Eleven of 12 argentaffin carcinoids could be immunostained with anti-Ser serum and all of those 11 were composed almost totally of Ser cells. One of the 11 contained a small number of Neu cells. Ultrastructurally, 11 argentaffin carcinoids were composed predominantly of EC1 and/or ECn cells, and one was composed primarily of non-EC cells. Out of the six argyrophil carcinoids, five were argyrophil, non-argentaffin carcinoids; three consisted almost totally of PYY cells; one consisted of 60% PYY cells, 40% So cells and a few Gli cells; and one consisted of Ser cells alone. Ultrastructurally, the first four of those tumors were composed of D1 and/or L cells and the latter tumor was composed of ECn cells. The remaining one argyrophil carcinoid contained a few Ser-positive argentaffin cells and consisted almost totally of ECn cells which were found in both parts, with and without argentaffinity. It is concluded that the appendiceal carcinoids comprise two distinct groups on the basis of the main constituting cell type: Ser-positive, argentaffin carcinoids, composed of EC cells and peptide (especially of PYY)-positive, and Ser-negative, argyrophil non-argentaffin carcinoids of D1 and/or L cells.

Adolescent↗
PubMed1989

Effects of superior mesenteric and coeliac ganglionectomy on peptide-producing cells of the small intestinal mucosa in the Hanford mini pig. II. Immunohistochemical study.

Superior mesenteric and coeliac ganglionectomy was performed in 5 Hanford mini pigs and cholecystokinin (CCK)-immunoreactive I-cells, neurotensin (NT)-immunoreactive N-cells, glucagon (Glu)-immunoreactive L-cells, glicentin (Glic)-immunoreactive L-cells and somatostatin (Som)-immunoreactive D-cells were quantitatively evaluated in the duodenum, the upper, middle and lower jejunum and the ileum before, 3 weeks and 6 months after ganglionectomy. Three additional animals served as controls. After ganglionectomy, I-cell numbers increase by 110% in the upper jejunum and duodenum; N-cells increase by 86% in the lower jejunum. Glu- and Glic-immunoreactive L-cells decrease slightly in the jejunum. In contrast, D-cells decrease in all sections of the small intestine by 44-76% (P less than 0.05 and P less than 0.001). All the examined entero-endocrine cells, except the D-cells in the duodenum and upper jejunum, develop hypertrophy after ganglionectomy. No changes either in number or size are found in the ganglia and neurons of the myenteric plexus. From these and the recently described increase in villus height and absorptive cells and absorptive cell enzymes after ganglionectomy (Holle, G.E. et al. Effects of superior mesenteric and coeliac ganglionectomy on the mucosa of the small intestine in the Hanford mini pig. I. Histological and enzymhistochemical study, J. Auton. Nerv. Syst., 26 (1988) 135-145), we conclude that the extrinsic nervous system takes suppressive influence on structure and probably function of the small intestinal mucosa by modifying its cellular organization.

Animals↗
PubMed1983

Immunocytochemical evidence for a substance related to the bovine pancreatic polypeptide-peptide YY group of peptides in the human fetal gastrointestinal tract.

The time of the first appearance and distribution of substance(s) reacting with the bovine pancreatic polypeptide (BPP) antiserum No. 146-6, i.e., BPP-like immunoreactivity, were studied in the gastrointestinal tract of 5-24-week-old human fetuses using an indirect immunoperoxidase method. The first immunostaining was identified at the 12th week of gestation in the oxyntic and colonic mucosa, and at the 10th week in the ileum. Serial sections alternately labelled with BPP and glicentin (GLI-1) antisera show several patterns. In the enteric and oxyntic mucosa, there is a cell population reacting only with the GLI-1 antiserum intermixed with cells containing both BPP-like and GLI-1-like immunoreactivities. In the oxyntic mucosa, however, certain cells might store BPP-like material only. Specificity tests illustrate cross-reactivity occurring in immunocytochemical studies of extrapancreatic BPP. The ability of synthetic BPP or a chemically related peptide, peptide YY to abolish the BPP antiserum immunoreaction, as well as previous radioimmunoassay data, raise the question of the presence of authentic BPP in GLI-1-containing cells.

Animals↗
PubMed1986

Inhibition of pentagastrin-stimulated gastric acid secretion by intraileal administration of bile and elevation of plasma concentrations of gut glucagon-like immunoreactivity in anesthetized dogs.

The effects of intraileal administration of bile on gastric acid secretion stimulated by a submaximal dose of intravenous pentagastrin infusion and on plasma concentrations of gut glucagon-like immunoreactivity (gut GLI) were studied in anesthetized dogs. Gastric acid secretion was measured for a 2-h period at 15-min intervals before and after intraluminal instillation of test solutions. 100 ml of canine bladder bile diluted to 10% in saline evoked a significant inhibition (20%) of gastric acid secretion. The inhibition of gastric acid secretion was accompanied by an elevation of plasma concentration of gut GLI, whereas saline instillation (in controls) caused no responses. Although the inhibition of gastric acid secretion and the elevation of plasma gut GLI are parallel phenomena, gut GLI can be reasonably postulated as one of the candidate mediators of bile-induced inhibition of gastric acid secretion, since its structurally related peptides, pancreatic glucagon, glicentin and oxyntomodulin have been reported as inhibitors of gastric acid secretion.

Animals↗
PubMed1988

Immunoreactive glucagons purified from dog pancreas, stomach and ileum.

Previous studies have shown that pig intestine contains a 69 amino acid glucagon (glicentin) as well as a 37 amino acid glucagon (oxyntomodulin). In pig pancreas the 29 amino acid glucagon predominates. Since glucagon is thought to be expressed from a single gene in mammals, these differences in molecular forms indicate differential posttranslational processing of the glucagon precursor by different tissues. In the current study glucagon immunoreactivity (IR) was separately purified from dog pancreas, stomach mucosa and ileum mucosa. Purification and sequence analysis of the different tissue glucagons show that dog pancreas and stomach mucosa contain glucagon-29 while ileum mucosa contains glucagon-37 and glucagon-69. The latter is the major form present with glucagon-37 accounting for only 10-20% of the total ileum glucagon content. The N-terminal 32 amino acid portion of dog glucagon-69 differs at 6 sites from pig glucagon-69: RSLQDTEEKSRSFSAPQTEPLNDLDQMNEDKR... The C-terminal glucagon-37 is identical to pig oxyntomodulin.

Amino Acid Sequence↗
PubMed1996

Adrenomedullin: localization in the gastrointestinal tract and effects on insulin secretion.

Adrenomedullin is a novel hypotensive adrenal polypeptide originally isolated from a human pheochromocytoma and is structurally related to calcitonin gene-related peptide and islet amyloid polypeptide. Using immunocytochemistry, the occurrence of adrenomedullin in the adrenal gland and gastro-entero-pancreatic region in the rat was examined and its effect on insulin secretion from isolated rat islets was determined. Adrenomedullin-like immunoreactivity occurred in noradrenaline- and adrenaline-producing cells in the adrenal gland. Gastrointestinal endocrine cells, with increased density distally, displayed adrenomedullin-like immunoreactivity; these cells constituted a subpopulation of the enterochromaffin (serotonin-containing) cells. Co-localization of adrenomedullin with somatostatin, glicentin, gastrin/cholecystokinin, peptide YY or islet amyloid polypeptide was not encountered. Adrenomedullin-immunoreactive cells were not observed in the pancreatic islets. At 1, 10 and 100 nmol/l, adrenomedullin stimulated insulin release from isolated rat islets in the presence of 3.3 mmol/l glucose (P < 0.05) and at 100 nmol/l, the peptide potentiated insulin secretion also in the presence of 8.3 mmol/l glucose (P < 0.05). These findings suggest that, besides being an adrenal hypotensive peptide, adrenomedullin may be a gut hormone with a potential insulinotropic function.

Adrenal Glands↗
PubMed1981

Evolutionary aspects of "brain-gut peptides": an immunohistochemical study.

Phylogeny of biogenic peptides and their source cells was studied by immunohistochemistry and electron microscopy. The distribution of the peptide containing neurons and paraneurons in the brain and in the gastroenteropancreatic endocrine system was depicted, especially in the bullfrog as the representative of deuterostomia and in the cockroach and some other insects as the representatives of protostomia. Stress was given to: (1) calcitonin-immunoreactive neurons in bullfrog hypothalamus and PP-reactive neurons in the cockroach protocerebrum as instances of transmissional-hormonal partition of a neuropeptide, (2) open-type endocrine cells in the gut structurally and functionally common to the protostomia and deuterostomia, and (3) phylogeny of the prohormones with special reference to big gastrin and proglucagon (glicentin).

Animals↗
PubMed1985

Phylogenetical aspects on islet hormone families: a minireview with particular reference to insulin as a growth factor and to the phylogeny of PYY and NPY immunoreactive cells and nerves in the endocrine and exocrine pancreas.

A common feature in the phylogeny of the four islet hormones (insulin, somatostatin, glucagon, PP) is that they do not seem to occur in the most primitive metazoan animals investigated so far, namely the coelenterates. However, already in the earliest protostomian invertebrates, such as flatworms and annelids, somatostatin and PP immunoreactive nerve fibres were found. In highly developed forms of protostomian invertebrates, such as insects, all the four islet hormones are represented as immunoreactive nerve cells and nerve fibres in the brain. In deuterostomian invertebrates a brain-gut-axis has evolved as regards somatostatin and PP, whereas insulin and glucagon now seem to occur exclusively as cells of open type in the gut mucosa. This brain-gut-axis for somatostatin and PP persists in all the vertebrates. The insulin cells, however, leave the gut mucosa already in the earliest forms of vertebrates and then appear only as cells in the islet parenchyma and in the mucosa of the bile duct (Agnatha) or in the pancreatic ducts (Gnathostomi). To some extent, glucagon islet cells evolve in a similar manner; here, however, cells immunoreactive with the precursor hormone, glicentin (enteroglucagon), persist in the gastrointestinal tract mucosa. A few PYY immunoreactive cells have been found in the pancreatic islet parenchyma of reptiles and mammals, often as disseminated cells in the acinar tissue. In the pancreas of these phyla NPY only occurs in neurons and nerve fibres. In pilot studies the effects of hagfish insulin as a growth factor have been compared with those of pig insulin on Swiss 3T3 mouse embryonic fibroblasts.

Animals↗