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)

The efficacy of subchronic (3 weeks) treatment with the long-acting somatostatin analogue octreotide was studied in four patients with symptomatic benign insulinoma. No clinical or biochemical effect on serum glucose, insulin, C-peptide or glucagon was observed in all four patients despite clearly detectable serum levels of octreotide. The resistance to octreotide therapy in these patients might be explained by the absence of somatostatin analogue receptors on their tumours.
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PMID:No effect of the long-acting somatostatin analogue octreotide in patients with insulinoma. 192 92

In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypoglycaemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (less than or equal to 2.3 mmol l-1) within 2-44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR-insulin) concentrations. IR-proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady-state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4-5.0 mmol l-1 was significantly (P less than or equal to 0.001) higher in insulinoma patients (2.5 +/- 0.6 mg kg-1 min-1) than in pancreas resected patients (0.6 +/- 0.2 mg kg-1 min-1), or in control subjects (0.5 +/- 0.1 mg kg-1 min-1). Due to a considerable degree of overlap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR-insulin values (r = 0.024, P = 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR-insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of 'amended' insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR-C-peptide plasma concentrations) by 52-88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de-differentiated tumours. In contrast to this significant (P = 0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal beta-granules, and does not distinguish adenomas from carcinomas.
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PMID:Evaluation of a euglycaemic clamp procedure as a diagnostic test in insulinoma patients. 196 48

Because of its widespread distribution within the nervous system and the gastro-enteropancreatic (GEP) system and its diverse physiological inhibitory actions on various gastrointestinal functions, including endocrine and exocrine secretion, motility, liver and splanchnic blood flow and absorption, native somatostatin has been viewed as a possible therapy for many diseases. However, its short duration of action and consequent limited clinical usefulness have been overcome with the availability of Sandostatin, a long-acting, synthetic octapeptide analogue of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of GH and TSH secreting pituitary tumours and GEP endocrine tumours (carcinoid tumour, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical in vitro and animal studies have shown the antineoplastic activity of the compound. Moreover, because of a possible direct effect on somatostatin receptor-positive endocrine tumour cells and indirect effect whereby Sandostatin lowers GH, IGF-1 and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labelling of somatostatin receptor-positive tumours with radiolabelled somatostatin analogues now allows localisation of such tumours and their metastases. Moreover, targeted irradiation of these tumours by beta particle emitting isotopes attached to such somatostatin analogues may become possible. The use of Sandostatin in acute oesophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal and pancreatic external fistulae, short bowel syndrome, dumping syndrome and AIDS-related refractory hypersecretory diarrhea has provided encouraging results. Preliminary reports indicate efficacy of Sandostatin in psoriasis, autonomic neuropathy (postprandial and orthostatic hypotension) and its ability to reduce height velocity in tall adolescents. The ultimate role of Sandostatin as a therapeutic agent in these disorders is being explored in prospective clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Future medical prospects for Sandostatin. 198 Jul 78

The newly developed long-acting somatostatin analogue SMS 201-995 was used to treat a patient with the presumptive diagnosis of benign insulinoma. Although intermittent injections with 50-100 micrograms s.c. every 8 h failed to produce any clinical improvement, continuous s.c. infusion with 150-300 micrograms/day prevented the hypoglycemic episodes absolutely, both during normal dietary intake and throughout 72 h of fasting. Chronic treatment (to date 30 months) has not been associated with any evidence of tachyphylaxis or rebound hypersecretion of insulin.
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PMID:Chronic treatment of a benign insulinoma using the long-acting somatostatin analogue SMS 201-995. 215 84

To investigate the relationship between surface ganglioside expression and pancreatic islet cell differentiation, we examined the function of five rat insulinoma (RIN-m5F) sublines A4, A6, A7, A10, and A12 selected for increased expression of A2B5-reactive gangliosides, as well as a subline AlGh, low in A2B5- but high in 3G5-reactive ganglioside expression. Class I major histocompatibility (MHC) protein expression was also measured in the sublines because of our previous finding that class I proteins were preferentially expressed on human insulinoma tissue compared with differentiated islet cells. In comparison with parental RIN-m5F cells, subline A12 displayed a 7.6-fold increase in A2B5 expression and a 3.4-fold increase in the number of A2B5 positive cells (81% vs. 24%). A2B5 expression was increased 1.3-, 5.4-, 5.4-, and 6.9-fold on A4, A6, A7, and A10 sublines, respectively. In contrast, AlGh cells, which had comparable A2B5 expression to parental cells, displayed a 2.9-fold increase in 3G5 expression and an 8-fold increase in the number of 3G5 positive cells (72% vs. 9%). Insulin secretion and content increased with increasing A2B5 expression. On day 2, secretion was 1.2-, 8-, 8-, 21-, and 18-fold higher and content 1.4-, 4-, 5-, 26-, and 33-fold higher for A4, A6, A7, A10, and A12 cells, respectively, compared to parental cells. There was a direct association between expression of A2B5 and the level of insulin messenger RNA (mRNA) in the sublines. Neither glucagon nor somatostatin was detected in any subline. The AlGh subline secreted and contained less insulin than parental cells. Fully differentiated adult rat islet cells, the majority of which are beta-cells, contained a lower number of 3G5 (12%) than A2B5 (57%) positive cells. Compared to parental cells, class I MHC proteins were decreased 4-fold on A12 cells, but increased 1.5-fold on AlGh cells. We conclude that, at least in RIN cells, the expression of A2B5-reactive ganglioside expression is associated directly, and class I MHC protein expression indirectly, with beta-cell differentiation.
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PMID:A2B5-reactive ganglioside expression is an index of differentiation in rat insulinoma (RIN) cells. 215 72

Transgenic mice bearing a fusion gene consisting of rat elastase I 5' flanking DNA fused to the early-coding (T-antigen) region of the SV40 genome (ELSV mice) develop carcinomas of the acinar cells of the exocrine pancreas. Histopathological examination of pancreatic tissue from 79 such animals revealed that, in addition to acinar cell neoplasms, ELSV mice develop two distinct lesions of the islets of Langerhans. By the age of 26 weeks, 36% of the mice had developed insulinomas. Starting at 8 weeks of age, the mice also developed D (somatostatin)-cell hyperplasia, which began at the periphery of the islets but which in advanced cases resulted in nearly complete replacement of other islet cell types by D-cells. By 26 weeks of age, 85% of the mice examined demonstrated the D-cell abnormality. Both the insulinomas and D-cell lesions were negative by immunohistochemistry for T-antigen, which was, however, demonstrated in acinar cell neoplasms using a monoclonal antibody against a C-terminal T-antigen epitope. Insulinomas have been described in other SV40 transgenic mice, particularly when the SV40 enhancer is not included in the transgene, suggesting that the presence of native SV40 enhancer may ordinarily suppress the expression of T-antigen in pancreatic beta-cells. The somatostatin-cell lesion is unique to the ELSV model; it may be neoplastic or represent a response to the growth and neoplastic changes occurring simultaneously in the exocrine pancreas.
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PMID:Hyperplasia and tumors of the islets of Langerhans in mice bearing an elastase I-SV40 T-antigen fusion gene. 216 83

The effects of octreotide in vivo and in vitro on hormone release, in vivo [123I]Tyr3-octreotide scanning, and in vitro [125I]Tyr3-octreotide autoradiography were compared in five patients with endocrine pancreatic tumors. [123I]Tyr3-octreotide scanning localized the primary tumor and/or previously unknown metastases in four of the five patients. The patient with a negative scan had an insulinoma that did not respond to octreotide in vivo. No Tyr3-octreotide-binding sites were subsequently found at autoradiography of the tumor, whereas somatostatin-14 receptors were present at a high density. In parallel, culture studies with the cells prepared from this adenoma showed that insulin release was not affected by octreotide, while both somatostatin-14 and -28 significantly suppressed hormone release. Culture studies of the tumor cells from two gastrinomas showed a dose-dependent inhibition of gastrin release by octreotide. Octreotide exerted direct antiproliferative effects in one of these gastrinomas, which had been shown to be rapidly growing in vivo. Both gastrinomas had specific somatostatin receptors, as measured by in vitro receptor autoradiography. Somatostatin release by the cultured somatostatinoma cells from one of these patients was suppressed by octreotide. In conclusion, 1) the [123I]Tyr3-octreotide scanning procedure is valuable in the localization of primary endocrine pancreatic tumors as well their often clinically not yet recognized metastases; 2) the in vitro detection of somatostatin receptors in those tumors that were also visualized in vivo after injection of [123I] Tyr3-octreotide indicates that the ligand binding to the tumor in vivo indeed represents binding to specific somatostatin receptors; and 3) the parallel between the presence of somatostatin receptors on tumors and in in vivo and in vitro effects of octreotide on hormonal release from these tumors indicate that a positive scan predicts a good suppressive effect of octreotide on hormonal hypersecretion by these tumors.
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PMID:Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: consequences with regard to diagnosis, localization, and therapy. 216 29

Because of its widespread distribution within the nervous system and gastroenteropancreatic (GEP) system, and its diverse physiological inhibitory actions on various gastrointestinal functions, including endocrine and exocrine secretion, motility, liver and splanchnic blood flow and absorption, native somatostatin has been viewed as a possible therapy for many diseases. However, its short duration of action and consequent limited clinical usefulness have been overcome with the availability of Sandostatin (octreotide, Sandoz Ltd), a long-acting, synthetic octapeptide analog of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of growth hormone (GH) and thyrotropin (TSH)-secreting pituitary tumors and GEP endocrine tumors (carcinoid tumor, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical in vitro and animal studies have shown the antineoplastic activity of the compound. Moreover, because of a possible direct effect on somatostatin receptor-positive endocrine tumor cells and an indirect effect whereby Sandostatin lowers GH, insulin-like growth factor type 1 (IGF-1), and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labeling of somatostatin receptor-positive tumors with radiolabeled somatostatin analogs now allows localization of such tumors and their metastases. In addition, targeted irradiation of these tumors by beta particle-emitting isotopes attached to such somatostatin analogs may become possible. The use of Sandostatin in acute esophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal, and pancreatic external fistulae, short bowel syndrome, dumping syndrome and acquired immunodeficiency syndrome (AIDS)-related refractory hypersecretory diarrhea has provided encouraging results.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Future medical prospects for Sandostatin. 220 87

Dissociated human insulinoma cells were plated onto plastic multiwell dishes. Cells were maintained for 1 mo on plastic with three passages. Cultures consisted of small colonies with some areas of stratification and few intercellular spaces. Ultrastructural studies indicated that cultured cells had epithelial features with desmosomes at cell-to-cell contacts and intermediate filaments in addition to secretory granules in the cytoplasm. Insulin and C-peptide were released in equimolar amounts in culture media. When challenged for 30 min with 16.7 mM glucose, 1 mM 3-isobutyl-1-methylxanthine, 4 mM tolbutamide, or 10(-6) M glucagon, insulinoma cells responded by a 1.5-, 1.5-, 2-, or 3-fold increase, respectively, in insulin release above baseline levels. A 15-min challenge with 10(-5) M isoproterenol increased insulin secretion by 1.85-fold. By indirect immunofluorescence, an anti-insulin antibody reacted positively with cell cytoplasm, whereas anti-somatostatin and anti-glucagon antibodies did not. Insulinoma cell surface expressed class I MHC molecules but not class II molecules. Immediately after isolation, crude insulinoma cells were contaminated by 2% of DR+ cells from nonislet components that disappeared after several weeks in culture. The ability of insulinoma cells to stimulate allogenic T-lymphocyte proliferation was assessed by [3H]thymidine incorporation in mixed culture combinations. Crude insulinoma cells elicited a strong lymphoproliferative response with a stimulation index ranging between 3.5 and 7, whereas no stimulation was found after 1 mo in culture. It is postulated that absence of class II-positive cells in the stimulatory cell preparation conditioned this immune tolerance across the major histocompatibility barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structure, function, and immunogenicity of human insulinoma cells. 245 30

Sandostatin (SMS 201-995 (SMS)), a potent, long acting analog of native somatostatin was used in five patients with functional endocrine tumors (gastrinoma, two patients; insulinoma, one patient; glucagonoma, one, and adult onset nesidioblastosis, one). Primary and secondary peptide levels were obtained during provocation with a test meal, a calcium infusion, a secretin bolus and either a glucagon or tolbutamide bolus. During provocation test, the levels of the primary peptides insulin and C-peptide (nesidioblastosis and insulinoma), gastrin (gastrinoma), glucagon (glucagonoma) and the secondary peptides calcitonin, gastrointestinal peptide, gastrin releasing peptide, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance-P and vasoactive intestinal peptide were obtained at predetermined intervals and quantitated by radioimmunoassay. SMS therapy was begun and peptide levels were again obtained during provocation. SMS suppressed basal primary peptide levels in all patients by more than 50 per cent. In 23 of 26 provocative tests, SMS effectively decreased circulating peptide levels by more than 50 per cent. Thirteen instances of elevated basal secondary peptides were discovered, and SMS universally suppressed these levels by a mean of 54 per cent. Of the 44 provocative tests performed, elevated secondary peptide levels were present in 41. SMS was effective in 31 of these 41 tests. The mean suppression of these provoked secondary peptide levels was 70 per cent. SMS effectively suppresses both basal and provoked peptides and, thus, provides relief of the clinical symptoms induced by pathologic elevations of primary and secondary peptides.
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PMID:Suppression of primary and secondary peptides with somatostatin analog in the therapy of functional endocrine tumors. 246 Sep 58


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