Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of glucagonoma syndrome with necrolytic migratory erythema, glossitis, anemia, hyperglucagonemia and a malignant, pancreatic A-cell tumour in a 68-year-old male is described. Gel filtration of the highly elevated circulating glucagon immunoreactivity (2200 pg/ml) demonstrated 60% pancreatic glucagon and 30% "proglucagon". Metabolic studies before operation demonstrated suppression of the total plasma glucagon concentration on oral glucose tolerance test, unchanged total plasma glucagon concentration during intravenous glucose tolerance test and insulin-induced hypoglycemia. Administration of arginine was followed by a rise in both the pancreatic glucagon and the "proglucagon", whereas alanine increased only the pancreatic glucagon. The plasma somatostatin level was immeasurable preoperatively. Somatostatin infusion completely suppressed the release of the pancreatic glucagon but did not significantly affect the "proglucagon". After removal of the tumour the skin lesions disappeared and the total plasma glucagon values fell to normal levels (120 pg/ml). Also, other abnormal laboratory findings returned to normal, including the preoperatively observed renal glucosuria.
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PMID:Metabolic studies and glucagon gel filtration pattern before and after surgery in a case of glucagonoma syndrome. 21 26

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.
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PMID:Radioimmunoassay in diagnosis, localization and treatment of endocrine tumours in gut and pancreas. 22 84

The endocrine function of the pancreas consists of the promotion of storage of nutritive substances after meals through the liberation of insulin and to guarantee the mobilization of this food energy through the secretion of glucagon during fasting. Increased hormone production may result from tumors of the islet cells (insulin: insulinoma; glucagon: glucagonoma; gastrin: Zollinger-Ellison syndrome). An absolute or relative insulin deficiency is a characteristic of diabetes mellitus, in which a relative hyperglucagonemia is also of possible pathophysiological significance. This increased secretion of glucagon can be suppressed by somatostatin. While the clinical application of somatostatin in diabetes mellitus seems problematic at present, the use of a glucose-controlled system of insulin infusion ("artificial pancreas") makes possible a metabolic state approaching the healthy condition.
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PMID:[The endocrine pancreas. From the isolated islet to the "artificial pancreas" (author's transl)]. 81 14

The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin (delta-cells), and pancreatic polypeptide (PP-cells) in a sequential order. The endocrine cells are believed to arise from a stem cell with neuronal traits. The developmental lineage from a common neuron-like progenitor is evidenced by: transient coexpression of more than one cell type-specific hormone in immature cells, expression of neuronal markers during islet cell development, and the pluripotentiality of clones of insulinoma cells to develop into cells expressing other islet cell hormones. The four mature endocrine cell types assume a particular organization within the islets of Langerhans in a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor. Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N-cadherin in brain. Insulinoma cells express E-cadherin but differ from primary islet cells by expressing a second cadherin molecule, which is similar to N-cadherin. The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype with strong neuronal traits, reflecting the early palce of glucagon-producing cells in the islet cell lineage. In contrast, insulinoma cells are more islet-like in their phenotype and show less neuronal traits.
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PMID:Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas. 140 10

We report the results of transcatheter intraarterial perfusion of liver with the emulsion of iodized oil and cytostatics performed as palliative treatment in three patients with hepatic metastases of pancreatic endocrine tumors. Two patients had insulinoma and one patient had glucagonoma. They were also treated by medical therapy from the time the diagnosis was made. Intraarterial perfusion of the liver was achieved by Lipiodol emulsified with streptozotocin and 5-fluorouracil. Regarding these three patients therapeutic responses were different in duration of hormone secretion decrease. Relief of hypoglycemic attacks and a significant decrease of plasma immunoreactive insulin concentration within 12 months without any additional therapy was observed in the patient with insulinoma (case no. 2). This patient had slightly increased immunoreactive glucagon concentration from the time of diagnosis. A decrease of immunoreactive insulin levels in other patient with insulinoma and an increase in plasma glucose to the euglycemic range during two months allowed a reduction of doses of somatostatin analogue and diazoxide. Due to rapid progression of the disease, intraarterial perfusion of liver was repeated three months later with the same results. Remission of symptoms was partial in the case of glucagonoma. Immunoreactive glucagon levels were not changed and there was no significant benefit of the treatment. Intraarterial perfusion of liver with iodized oil and cytostatics could be an effective, safe and repeatable method of palliating symptoms of malignant pancreatic tumors, especially in inoperable but nonterminal cases. It could allow reduction of additional medical therapy, but success of the treatment is not predictable.
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PMID:Improvement of metastatic endocrine tumors of the pancreas by hepatic artery chemoembolization. 144 92

Pancreatic tumours of transgenic mice carrying a glucagon-promoted simian virus 40 (SV40) T antigen oncogene have been analysed by histological, histochemical, ultrastructural and radioimmunological means. Seven transgenic mice were examined revealing dysplastic and neoplastic lesions in the endocrine pancreas. Four tumours were identified, one of which metastasized to periadrenal spaces and paravertebral lymph nodes. Benign tumours were composed of argyrophilic, endocrine cells reactive to a range of antibodies against neuroendocrine markers (neuron-specific enolase, protein gene product 9.5, chromogranin A, synaptophysin and protein 7B2) and different fragments of the proglucagon molecule (glucagon, glicentin, glucagon-like polypeptides 1 and 2). A few tumour cells expressed pancreatic polypeptide, somatostatin or insulin. Conventional ultrastructural analysis and immunogold labelling revealed typical glucagon-immunoreactive alpha granules which co-stored glicentin and glucagon-like polypeptides 1 and 2. The malignant primary tumour and its metastases were composed mainly of cells which did not show immunoreactivity for neuroendocrine markers or peptides. Atypical, glucagon-immunogold labelled granules were detected at electron microscopy in differentiated tumour cells and C-type retroviral particles in the largest tumour population of degranulated cells. The transgene-encoded oncoprotein SV40 large T-antigen was detected in the nuclei of well-differentiated tumour cells and in alpha cells of some dysplastic islets. All tumour-bearing mice showed high levels of circulating glucagon-like immunoreactivity. Transgenic mice harbouring the glucagon-promoted SV40 T antigen oncogene may provide a model for human glucagonoma.
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PMID:Glucagonomas of transgenic mice express a wide range of general neuroendocrine markers and bioactive peptides. 167 63

The non-tumoral endocrine pancreas from a patient with elevated plasma levels of glucagon due to a malignant glucagonoma was studied immunocytochemically, ultrastructurally and morphometrically. Compared with normal pancreatic islets from control subjects, those of the pancreas from the patient with a glucagonoma showed an almost complete disappearance of A cells, a decrease in immunoreactive insulin in B cells associated with cytological features indicating enhanced synthesis and secretion of this hormone, and an increase in immunoreactive somatostatin and pancreatic polypeptide (PP) accompanied by unusually high numbers of D and PP cells. In addition, numerous B cells were found outside the islets, either forming micro-islets or scattered in the exocrine tissue (nesidioblastosis). The possible mechanisms involved in determining the changes in the secretory activity of B cells and the alterations in the cell composition of the islets are discussed.
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PMID:Morphological changes in the human endocrine pancreas induced by chronic excess of endogenous glucagon. 167 71

The therapeutic principles in the management of endocrine gastroenteropancreatic (GEP) tumours include surgical extirpation of the primary tumour in the absence of metastases and medical control of symptoms in the preoperative phase. In the presence of metastases only palliative procedures are available. Tumour growth might be controlled by surgical procedures as debulking of tumour masses, medically by chemotherapy and more recently by new developments as a long-acting somatostatin analogue (SMS 201-995) and alpha-interferon. Their efficacy is currently evaluated in prospective studies. In contrast to inhibition of growth symptoms derived from excessive hormone production by GEP tumours can be well controlled. SMS 201-995 effectively prevents or at least improves flush and diarrhoea in the carcinoid syndrome, disabling diarrhoea in the Verner-Morrison syndrome and migratory erythema in the glucagonoma syndrome. SMS acts by inhibition of hormone release from the tumour and by a direct mechanism at the site of the target cell via SMS receptors present on tumour and target cells. For control of acid hypersecretion in gastrinoma patients omeprazole is superior to all former and present alternatives and replaced total gastrectomy completely. A similarly effective drug to prevent hypoglycaemia due to uncontrolled insulin release from insulinomas is not available since neither SMS nor diazoxide are effective in every insulinoma patient.
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PMID:Therapeutic strategies in the management of endocrine GEP tumours. 170 88

The glucagonoma syndrome is characterized by elevated serum glucagon, a pancreatic alpha-cell tumor, anemia, hypoaminoacidemia, and necrolytic migratory erythema. Necrolytic migratory erythema may cause marked morbidity and is frequently misdiagnosed. A 42-year-old white woman with a 1 1/2-year history of refractory dermatitis (most severe on the lower extremities) had the glucagonoma syndrome. Her severe morbidity was markedly relieved with the administration of intravenous amino acids. This therapy was successful in controlling the necrolytic migratory erythema through recurrences after somatostatin (SMS 201-995), surgical debulking, and chemotherapy proved inadequate.
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PMID:Treatment of necrolytic migratory erythema in glucagonoma syndrome. 176 71

The pancreatic beta-cell is a major site of islet amyloid polypeptide (IAPP) biosynthesis, and the peptide is coreleased with insulin. We have analyzed the expression of IAPP (mRNA and protein) in various cell types in normal and transformed murine islet cell cultures by Northern blot analyses and immunocytochemistry. IAPP is primarily coexpressed with insulin in the beta-cell of GH-promoted primary rat islet cell cultures. Additionally, a small population of non-beta-cells exhibited a prominent IAPP expression, and double staining experiments showed colocalization with glucagon or somatostatin in some of these cells. IAPP mRNA was confined to the beta-cell phenotype when analyzing the phenotypically stable in vivo tumor lines, MSL-G2-IN (insulinoma) and MSL-G-AN (glucagonoma), and the transgenic mouse islet cell lines, beta-Tc and alpha-Tc. However, IAPP and insulin expression were completely uncoupled in unstable heterogeneous clones such as NHI-6F. This clone is composed of primarily glucagon-producing cells in vitro, but insulin gene expression becomes dominant after passage in vivo. Interestingly, IAPP was hyperexpressed with glucagon under in vitro conditions in this clone. We conclude that the tissue specificity of expressions of IAPP and insulin are controlled differently, and that coexpression of IAPP with hormones different from insulin may be a marker for pluripotent transformed rat islet cell clones, which are able to activate insulin gene transcription during passage in vivo.
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PMID:Islet amyloid polypeptide and insulin expression are controlled differently in primary and transformed islet cells. 185 Jan 7


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