Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence, morphology and distribution of anal neuroendocrine cells were investigated with a panel of antisera and antibodies for neural markers, biogenic amines, and neuropeptides by the sensitive streptavidin-biotin-peroxidase immunocytochemistry, and coexistence patterns of neurochemically characterized neuroendocrine cells were examined by double immunofluorescence cytochemistry. In the colorectal zone, endocrine-like cells were immunoreactive for chromogranin A (CGA), serotonin (5-HT), pancreastatin (PST), peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and somatostatin (SOM). Coexistence patterns of endocrine-like cell phenotypes with CGA and GLP-1 were heterogeneous. In the anal transitional zone (ATZ), endocrine-like cells were immunoreactive for CGA, 5-HT and PST. Furthermore, six new phenotypes of endocrine-like cells were characterized by their immunoreactivity for PYY, GLP-1, protein gene product 9.5 (PGP), calcitonin gene-related peptide (CGRP), neurotensin (NT), and SOM. All endocrine-like cell types in the ATZ were immunoreactive for CGA. In the squamous zone and perianal skin, CGA-immunopositive Merkel cells were also immunoreactive for CGRP, PST, NT and PGP. Neuroendocrine cells in the anal canal exhibit epithelial zone-related diversities in their neurochemical phenotypes and coexistence patterns, which may indicate specific regulatory functions. In the epithelium of the ATZ, which is regarded as metaplastic, endocrine-like cells expressed phenotypes characteristic of the neuroendocrine cells of the colorectal zone and the squamous zones, indicating a possible metaplastic origin of these cells.
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PMID:Distribution and chemical phenotypes of neuroendocrine cells in the human anal canal. 771 84

The development of diabetic ketoacidosis is an unusual complication of a glucagon-secreting pancreatic islet cell neoplasm, with only four reported cases in the literature. In this article, the authors report on a 46-year-old woman with a glucagonoma cosecreting pancreatic polypeptide, somatostatin, and serotonin diagnosed 8 months before the onset of diabetic ketoacidosis. She was treated with hydration, insulin, and octreotide, with improvement in her clinical course and a decrease in the glucagon, pancreatic polypeptide, and chromogranin A plasma levels. With the addition of weekly 5-FU, she has maintained a partial radiographic response and has had no further episodes of diabetic ketoacidosis for a 4.5-year period. Diabetic ketoacidosis can develop in the presence of a glucagonoma, and the pathophysiology remains unknown.
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PMID:Case report: diabetic ketoacidosis in a patient with glucagonoma. 777 3

Enterocolitis (EC) remains the most serious complication of Hirschsprung's disease (HD). The aetiology of EC is uncertain. Ischemic and bacterial causes, and recently rotavirus infection, have been suggested to explain the occurrence of EC. The gut has an abundance of neuroendocrine (NE) cells which modulate gut function by endocrine, paracrine, or neurocrine routes. We studied NE cell populations in the bowel from 16 patients with HD (six of whom had clinical evidence of EC) and rectal tissue from 6 controls. Immunohistochemical studies were carried out using monoclonal and polyclonal antibodies against chromogranin A, synaptophysin (general markers of NE cells), 5-Hydroxytryptamine (5-HT), somatostatin, peptide YY (PYY), and glucagon/glicentin (neuropeptides). The six patients who had clinical evidence of EC prior to defunctioning colostomy showed histological evidence of EC in the defunctioned bowel. Using immunocytochemistry and serial tissue sectioning it was found that the number of NE cells in the aganglionic segment of colon in patients with HD was significantly (P < .05) increased compared with the numbers in the ganglionic segment. However, in the ganglionic colon, there was a significant (P < .05) reduction in NE cells in EC patients compared with non-EC patients. These results were seen both with the generic endocrine cell marker chromogranin A, which stains virtually all endocrine cells, and with specific markers for 5-HT, PYY, and glucagon/glicentin, which identify distinct subpopulations of endocrine cells. These differences may be partially responsible for previous conflicting reports of NE cell distribution in HD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional reduction in intestinal neuroendocrine cell populations in enterocolitis complicating Hirschsprung's disease. 790 60

1. In postganglionic sympathetic neurones and adrenal chromaffin cells, catecholamines are co-stored in vesicles with soluble peptides, including chromogranin A (CgA) and neuropeptide Y (NPY), which are subject to exocytotic co-release with catecholamines. 2. Plasma catecholamine, CgA and NPY responses to stimulators and inhibitors of sympatho-adrenal catecholamine storage and release were measured in humans. Short-term, high-intensity dynamic exercise, prolonged low-intensity dynamic exercise, and assumption of the upright posture, in decreasing order of potency, predominantly stimulated noradrenaline (NA) release from sympathetic nerve endings. Only high-intensity exercise elevated CgA and NPY, which did not peak until 2 min after exercise cessation. Stimulated NA correlated with plasma CgA 2 min after exercise, and with NPY 5 min after exercise. 3. Insulin-evoked hypoglycaemia and caffeine ingestion, in decreasing order of potency, predominantly stimulated adrenaline (AD) release from the adrenal medulla. During insulin hypoglycaemia AD and CgA rose, but NPY was unchanged. Neither NPY nor CgA were altered by caffeine. The rise in CgA after intense adrenal medullary stimulation was greater than its rise after intense sympathetic neuronal stimulation (1.4-versus 1.2-fold, respectively). 4. Infusion of tyramine, which disrupts sympathetic neuronal vesicular NA storage, elevated systolic blood pressure and NA, while NPY and CgA were unchanged. After reserpine, another disruptor of neuronal NA storage, NA transiently rose and then fell; NPY and CgA were unaltered. After the non-exocytotic adrenal medullary secretory stimulus glucagon. AD rose while NA, CgA and NPY did not change. After amantadine, an inhibitor of protein endocytosis, both CgA and fibrinogen rose, while NA and NPY remained unaltered. Neither CgA, NPY, nor catecholamines were altered by the catecholamine uptake and catabolism inhibitors desipramine, cortisol, and pargyline. 5. Human sympathetic nerve contained a far higher ratio of NPY to catecholamines than human adrenal medulla, while adrenal medulla contained far more CgA than sympathetic nerve. 6. It is concluded that peptides are differentially co-stored with catecholamines, with greater abundance of CgA in the adrenal medulla and NPY in sympathetic nerve. Activation of catecholamine release from either the adrenal medulla or sympathetic nerves, therefore, results in quite different changes in plasma concentrations of the catecholamine storage vesicle peptides CgA and NPY. Only profound, intense stimulation of chromaffin cells or sympathetic axons measurably perturbs plasma CgA or NPY concentration; lesser degrees of stimulation perturb plasma catecholamines only. Neither CgA nor NPY are released during non-exocytotic catecholamine secretion.
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PMID:Sympatho-adrenal secretion in humans: factors governing catecholamine and storage vesicle peptide co-release. 792 73

In the endocrine pancreas, chromogranins A and B as well as secretoneurin (a biologically active peptide processed endoproteolytically from secretogranin II) are most intensely expressed in alpha (glucagon) cells. We examined whether the functional status of neoplastic and nonneoplastic human alpha cells is reflected in the expression patterns of chromogranins/secretogranins. Neoplastic alpha cells were analysed immunocytochemically in six functioning glucagonomas and 37 nonfunctioning neuroendocrine tumours (29 with alpha cells) for their immunoreactivity to chromogranin A and B, as well as secretoneurin. There was no difference in the staining intensity for either peptide between glucagonomas and nonfunctioning, alpha cell containing tumours. Nonneoplastic alpha cells from patients with a functioning glucagonoma showed a decreased glucagon immunoreactivity, whereas the expression of chromogranin A (but not chromogranin B and secretoneurin) was as intense as in alpha cells not associated with glucagonoma syndrome. These results suggest that the expression of chromogranins/secretogranins in neoplastic alpha cells of the pancreas may be independently regulated from the cells' functional status. In nonneoplastic alpha cells there seems to be an association between glucagon production and chromogranin B and secretoneurin expression.
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PMID:Expression of chromogranin A and B and secretoneurin immunoreactivity in neoplastic and nonneoplastic pancreatic alpha cells. 795 97

Novel monoclonal antibodies to human chromogranin A (CgA) and chromogranin B (CgB) were used to investigate the presence of immunoreactive (-IR) elements in the alimentary tract of the green frog Rana esculenta. Numerous CgA-IR and a few CgB-IR endocrine cells were found within the gut mucosa, from the oesophagus to the cloaca, with some local differences in density. Co-localization studies demonstrated that they were co-stored in almost all the serotonin-IR, the amylin-IR or islet amyloid polypeptide-IR cells and in the peptide tyrosine tyrosine-IR cells located proximal to the pylorus, but not in those located in more caudal tracts. No other co-localization was demonstrated; substances investigated included somatostatin, substance P, gastrin/cholecystokinin, glucagon, glycentin, bombesin, secretin and neurotensin. CgA-IR and CgB-IR cells nearly always displayed argyrophilia with the Grimelius silver method.
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PMID:Immunohistochemical localization of chromogranin A and B in the endocrine cells of the alimentary tract of the green frog, Rana esculenta. 808 25

The occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial-cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA-positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA-positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon-like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA-positive tumors tended to be more aggressive than CGA-negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar-cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin-producing tumors showed intermediate behavior.
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PMID:Endocrine cells in colorectal adenocarcinomas: incidence, hormone profile and prognostic relevance. 810 Aug 8

Clinicopathological and immunohistochemical analyses were performed on ten samples of gastrointestinal carcinoids resected in Ishikawa Prefectural Central Hospital. All samples showed positive reaction to chromogranin A. Serotonin was detected in 8 samples, somatostatin in 4 samples, gastrin in 2 samples. Glucagon/Glicentin in 1 sample, and PYY production in 2 samples. CEA production was detected in 8 samples, and microvascular invasion was observed in 6 of these 8 patients. The PCNA/cyclin labeling index (L.I.) of the cases with metastases was significantly higher than those without metastases. In conclusion, the expression of CEA and the PCNA/cyclin L.I. may be useful markers of the malignant potential of carcinoid tumors.
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PMID:Immunohistochemical analysis of gastrointestinal carcinoids. 810 55

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 micrograms/l (normal < 0.2) and within 2 days 3 x 200 micrograms octreotide daily suppressed plasma glucagon to 2.2-2.5 micrograms/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal < 0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4 x 600 micrograms/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preoproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.
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PMID:The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth. 818 58

The authors review the biochemical and biological properties of chromogranins and pancreastatin. Chromogranins A, B and C are acidic proteins of a molecular mass of 48,000, 76,000 and 67,000, respectively, located in the secretory granules of the neuroendocrine cells. Since large amounts of chromogranin A were found in most neuroendocrine tumours, chromogranin A plasma determination is a diagnostic tool even in silent tumours. Pancreastatin is a peptide derived from chromogranin A, which inhibits insulin secretion, exocrine pancreatic secretion and gastric acid secretion, and which stimulates glucagon secretion. Pancreastatin has different molecular forms, the major form being a high molecular form of 92 amino acids, found by the authors in human stomach- and colon extracts and in a liver metastasis of a gastrinoma. The controlled proteolysis of chromogranin A in gut neuroendocrine cells generates predominantly the high molecular weight form.
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PMID:Current status on chromogranin A and pancreastatin. 826 67


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