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 60-year-old patient developed signs and symptoms of glucagonoma syndrome (dermatitis, weight loss, anemia and hypoaminoacidemia). However, diabetes mellitus was absent. Glucagonoma was suspected because of markedly elevated plasma glucagon levels and the tumor was subsequently removed by surgery. Acidethanol extraction of the tumor and immunohistochemistry provided evidence of the presence of all four islet hormones, particularly that of glucagon and pancreatic polypeptide and to a lesser extent of somatostatin and insulin. Immunohistochemistry of the tumor (but not plasma) also showed the presence of alpha-HCG. Plasma glucagon immunoreactivity consisted to a large extent (approx. 90%) of a high molecular form of glucagon, probably proglucagon. In spite of the presence of alpha-HCG - which is assumed to be a marker of malignancy - the patient has been free of recurrence for the 2 1/2 years since surgery. The increasing number of cases reported during the past few years demonstrates that the syndrome is more common than previously suspected. Glucagon secretion and its typical clinical picture may be a valuable marker of a multihormonal pancreatic tumor. In a case of suspected glucagonoma, diagnosis can be established simply by obtaining a plasma glucagon level measurement.
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PMID:[Glucagonoma syndrome in a multihormonal pancreatic tumor]. 628 78

The place of the long-acting somatostatin analogue octreotide in the management of symptoms in patients with functional gastroenteropancreatic (GEP) tumors and of growth in patients with metastatic disease is reviewed in this report. Numerous studies indicate that octreotide is, currently, the therapeutic principle of first choice in the symptomatic treatment of patients with carcinoid syndrome, Verner-Morrison syndrome and glucagonoma syndrome but not of insulinoma and gastrinoma patients. A beneficial effect on tumor growth has been demonstrated in 40% of patients with metastatic GEP tumor with stabilization of the disease as the most favorable response. However, further studies have to identify subgroups of patients in whom octreotide alone or in combination with alpha-interferon inhibits tumor growth.
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PMID:Management of gastroenteropancreatic endocrine tumors: the place of somatostatin analogues. 769 32

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

We characterized somatostatin receptors expressed in hamster glucagonoma INR1G9 cells and the effects of somatostatin on glucagon secretion, proglucagon gene expression, and the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent signal-transduction cascade. 125I-labeled somatostatin was displaced by somatostatin-14 and somatostatin-28 with a dissociation constant of 2 nmol/l. Stable GTP analogues decreased binding of 125I-somatostatin to its receptors, suggesting an interaction of somatostatin receptors with G proteins. Chemical cross-linking of 125I-somatostatin to its receptor revealed a molecular mass of the ligand-receptor complex of 47 kDa. Somatostatin inhibited forskolin-stimulated activation of adenylate cyclase [2.5 microM forskolin (161%) + 1 microM somatostatin (128%); P < 0.05] and protein kinase A [10 microM forskolin (143%) + 1 microM somatostatin (114%); P < 0.05] but did not influence basal activities of these enzymes. Forskolin-induced stimulation of cAMP generation was reduced by somatostatin [2.5 microM forskolin (306%) + 1 microM somatostatin (145%); P < 0.05]. Somatostatin inhibited forskolin, theophylline, and arginine stimulation of glucagon secretion. Basal as well as forskolin-, theophylline-, and isobutyl methylxanthine-induced proglucagon gene expression was significantly reduced by somatostatin. Our data show that, in INR1G9 cells, somatostatin receptors are at least in part coupled to the adenylate cyclase system. Somatostatin is a potent negative regulator of both basal and forskolin-stimulated proglucagon gene expression. The interaction with forskolin occurs at the level of adenylate cyclase. The effect of somatostatin on basal proglucagon gene transcription is most probably mediated by an unrelated second messenger system. Somatostatin may influence several functions of the pancreatic A cell.
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PMID:Functional characterization of somatostatin receptors expressed on hamster glucagonoma cells. 784 Jan 80

It was the aim of the present study to examine whether 111In-pentetreotide, a somatostatin analogue with predominantly renal excretion, is a suitable receptor agonist for scintigraphic imaging of endocrine gastro-entero-pancreatic (GEP) tumors, and to evaluate the contribution of the usual imaging times 4 and 24 h p.i. In 36 patients, planar scintigrams obtained 4 h, and 24 h after i.v. injection of 111 or 222 MBq 111In-pentetreotide were compared to the results of other imaging procedures and of surgery. Single photon emission computed tomography (SPECT) was also performed 24 h p.i. Positive scintigraphies were obtained in 32 out of 36 patients (18/19 patients with carcinoid syndrome, 8/9 with non hormone-producing endocrine GEP tumors, 2/4 with gastrinomas, 1/1 with glucagonoma, 1/1 with a VIPoma, 2/2 with paragangliomas). In 9 patients tumor manifestations previously not detected by conventional imaging procedures were disclosed by 111In-pentetreotide scintigraphy. 24-h images yielded significantly more true positive findings than 4-h images. In 4 patients liver metastases missed on planar scans were detected by SPECT. A discrepancy between patient-based and organ-based analysis of the results was encountered thus indicating a possible intraindividual heterogeneity in somatostatin receptor expression. In conclusion, 111In-pentetreotide is a suitable somatostatin analogue for scintigraphic in vivo demonstration of somatostatin receptors and for imaging of most tumor manifestations in patients with endocrine GEP tumors. Further studies will have to evaluate whether or not a positive receptor scintigraphy predicts response to treatment with long-acting somatostatin analogues.
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PMID:111In-pentetreotide (somatostatin analogue) scintigraphy as an imaging procedure for endocrine gastro-entero-pancreatic tumors. 797 60

The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors.
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PMID:Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. 813 73

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 purpose of the workshop was to critically evaluate the use of octreotide in the management of important surgical and gastroenterological conditions. The topics covered included: (1) management of functioning gut neuroendocrine tumors, (2) new approaches to localize these tumors, (3) the place of octreotide in the treatment of variceal bleedings, and (4) the use of octreotide in postoperative conditions. Octreotide therapy has been shown to be effective in the carcinoid syndrome, in which symptom control is achieved in 85% of patients, and reduction in 5-HIAA in 60%. Although tumor regression is rarely seen, prolongation of survival probably occurs. Control of diarrhea has been achieved in 84% of patients with VIPoma treated with octreotide. Similarly, octreotide has been found to provide effective control of the necrolytic, migratory dermatitis seen in glucagonoma. By contrast, insulinomas are more resistant to somatostatin agonist therapy. In the Zollinger-Ellison syndrome, octreotide is effective in alleviating symptoms and in reducing serum gastrin levels. However, its use in this syndrome has been superceded by omeprazole. Radioiodine-labelled octreotide has been very effective in in vivo imaging of neuroendocrine tumors in the abdomen, and is now considered the best available technique for localizing these tumors preoperatively. Intraoperative localization with a hand-held gamma camera is being developed. There is an exciting future possibility to use the technique to deliver therapy to tumors. Octreotide therapy has been shown to be at least as effective as and without the adverse hemodynamic effects of Pitressin in control of variceal hemorrhage. It should be regarded as one of several modalities of therapy in the condition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin analogue therapy in functioning neuroendocrine gut tumors. 835 71

Various tumors of neuroendocrine origin that have amine precursor and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous injection of the somatostatin analogue [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks in its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]-octreotide) was developed. This analogue is excreted mainly via the kidneys, 90% of the dose being present in the urine 24 h after injection. Using 111In-octreotide scintigraphy, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, 3 out of 3 unclassified apudomas, but none out of 18 exocrine pancreatic carcinomas were visualized. Also, 19 out of 19 carcinoids, 15 out of 15 glomus tumors, 8 out of 12 medullary thyroid carcinomas, 6 out of 6 small cell lung carcinomas, 4 out of 4 growth hormone-producing and 6 out of 9 clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD-cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied to visualize breast cancer, lymphomas and granulomas. In 39 out of 50 patients with breast carcinoma, 10 out of 11 patients with non-Hodgkin lymphomas, 3 out of 3 patients with Hodgkin's disease, and 8 out of 8 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:111In-octreotide scintigraphy in oncology. 835 73

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.
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PMID:The glucagonoma syndrome. Clinical and pathologic features in 21 patients. 860 27


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