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 clinical presentation of Zollinger-Ellison syndrome (ZES) is the result of gastrin hypersecretion and may be modified by secondary peptide hypersecretion. Treatment is medical (H2-blockers) or surgical (tumor excision and total gastrectomy). H2-blocker escape occurs up to 23 per cent and surgical mortality ranges to 15 per cent. Treatment of advanced disease has limited success. Sandostatin (SMS 201-995) has been shown to decrease basal gastrin and gastric acid secretion in ZES. We hypothesized that SMS would suppress basal and provoked gastrin and secondary peptide secretion in ZES. A patient with refractory, metastatic gastrinoma underwent provocative testing (test meal, calcium infusion, secretion bolus and tolbutamide bolus). Thirteen peptides were drawn at set intervals during these provocative tests. Testing was repeated during SMS therapy (100 micrograms subcutaneously three times per day). Gastrin, pancreatic polypeptide (PP) and glucagon levels were elevated at baseline. SMS suppressed all three peptides (mean 74 per cent) (p less than 0.05). Gastrin, PP and glucagon were provoked by all four tests (means above baseline, 19, 155 and 138 per cent, respectively). Gastrin-releasing peptide, gastric inhibitory peptide and insulin were provoked by calcium infusion (427, 306 and 162 per cent above baseline, respectively). SMS suppressed 14 of 15 of these peaked-provoked peptide levels (mean 72.5 per cent, p less than 0.05). Gastric analysis during calcium infusion showed SMS suppression of hourly gastric secretory volume by 77.5 per cent and of acid production (milliequivalents of acid) by 87.5 per cent. During a 20 month follow-up period, the patient was maintained on SMS, 200 micrograms subcutaneously three times per day. She has remained asymptomatic. Interval peptide profiles at two, eight and 18 months show normal gastrin, PP and glucagon levels. A computed tomographic scan at eight months shows a remarkable regression of primary and metastatic tumor. Regrowth, however, was noted at 19 months. SMS may be useful in ZES by suppressing basal and provoked gastrin and secondary peptide secretion and may occasionally give palliation by yielding temporary tumor registration.
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PMID:Effect of somatostatin analog on peptide release and tumor growth in the Zollinger-Ellison syndrome. 218 84

In the present study of 45 patients with Zollinger-Ellison syndrome, the frequency and clinical importance of the release of multiple gastrointestinal peptides were assessed prospectively. During an initial evaluation, extent of gastrinoma, clinical symptoms, disease duration, and presence or absence of multiple endocrine neoplasia, type I (MEN-I) were assessed. All patients had determinations of fasting plasma gastrin, human pancreatic polypeptide, motilin, neurotensin, and somatostatin; 35 had determinations of insulin and gastrin-releasing peptide and 21 had determinations of glucagon. A plasma elevation of additional peptides besides gastrin was detected in 62%, with 44% having one, 18% having two, and 0% having three additional peptides elevated. Motilin was elevated in 29%, human pancreatic polypeptide in 27%, neurotensin in 20%, and gastrin-releasing peptide in 10%, whereas insulin, glucagon, and somatostatin were not elevated in any patient. The presence or absence of elevation of any peptide did not differ in patients with or without MEN-I, with gastrinoma size, with the presence or absence of metastatic disease, or with various clinical symptoms. Patients were assessed yearly for clinical evidence of a secondary symptomatic pancreatic endocrine tumor syndrome with a median follow-up of 146 and 84 months from onset or diagnosis, respectively. Only one patient (2% of patients) developed a second syndrome (rate, 2 patients per 100 patients observed for 10 years). These results demonstrate that the plasma elevation of multiple gastrointestinal peptides is common in patients with Zollinger-Ellison syndrome; however, the rate of developing a second symptomatic pancreatic endocrine tumor syndrome is much lower than generally believed. Furthermore, no evidence is found to support the conclusions that the detection of the plasma elevation of these peptides is clinically important in assessing MEN-I status, disease extent, or presence of metastatic disease or that elevated levels of motilin, neurotensin, gastrin-releasing peptide, or human pancreatic peptide are associated with any distinct clinical symptoms. Therefore, we recommend that plasma concentrations of these additional gastrointestinal peptides should not be assessed routinely but rather only if new symptoms develop.
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PMID:Multiple hormone elevations in Zollinger-Ellison syndrome. Prospective study of clinical significance and of the development of a second symptomatic pancreatic endocrine tumor syndrome. 222 72

The nuclear DNA content of 17 pancreatic neuroendocrine tumors was measured from paraffin-embedded tissue with flow cytometry. The tumors were classified by immunostaining with antisera for synaptophysin, insulin, gastrin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal polypeptide. Eight (47%) of the 17 tumors were aneuploid, and two (12%) were multiploid (had two aneuploid stemlines of cells). Seven of the eight insulinomas, one of the four gastrinomas, and two of the four nonspecified neuroendocrine tumors had an abnormal nuclear DNA content. The DNA indices of the aneuploid and multiploid cases ranged from 1.13 to 1.93, and three cases had a DNA index greater than 1.50. During the follow-up for up to 16 years (mean, 7 years), one patient with diploid nonspecified tumor died of the disease, another patient with a multiploid gastrinoma had metastatic disease develop, and a third patient with a multiploid nonspecified tumor was alive with the disease. The authors conclude that many neuroendocrine tumors of the pancreas have an abnormal nuclear DNA content as measured by DNA flow cytometry. DNA multiploid pancreatic neuroendocrine tumors may be associated with a less favorable clinical course, but this needs to be confirmed in additional studies.
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PMID:DNA ploidy in pancreatic neuroendocrine tumors. 234 35

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

The clinical, microscopic, immunohistochemical and ultrastructural features of 7 gastrinomas and 1 combined carcinoma-carcinoid tumor were evaluated. The tumors were located in the pancreas or duodenal wall in 6 cases, and on extragastro-enteropancreatic sites in 2 (liver or peripancreatic lymph node). All patients had the Zollinger-Ellison syndrome, 3 of them with additional bleeding and 1 with diarrhea. One patient with gastrinoma had additional tumors characteristic of the MEN-I syndrome. Immunohistochemistry showed gastrin and neuron-specific enolase-positivity in all of the tumors. Somatostatin was found in 4 cases, and single cell glucagon, pancreatic polypeptide. S-100 protein, keratin as well as carcino-embryonic antigen positivity in another few. Additional hormone production did not appear to be connected with biological behaviour of the tumors or with the clinical symptoms.
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PMID:Studies into gastrinomas and combined carcinomatous carcinoid tumors. Optical light- and electron microscopy and immunohistochemistry. 248 34

The long-acting somatostatin (SMS) analog, SMS 201-995 has beneficial effects on APUDomas. In two Zollinger-Ellison syndrome (ZES) patients we assessed basal acid output (BAO) and 24-h pH under SMS and compared them to controls. We also assessed total gastrin, gastrin 17, insulin, glucagon, C-peptide, and SMS by radioimmunoassay. In the benign gastrinoma, an acid-controlling action of SMS was shown, elevating the 24-h pH threshold over the pH range 1.5-5 of 55-10% compared with control. A parallel inhibition of the gastrins greater than 90% was apparent. We found no beneficial effect on gastric acid secretion and on tumor gastrin in the malignant gastrinoma despite a fourfold higher plasma SMS level. Non-tumor-related peptides were suppressed by approximately 50% and in contrast to gastrin they again reached pre-SMS levels before the next dose of the drug. We conclude that SMS is more effective in benign than in malignant gastrinomas, and may be exclusively so.
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PMID:Long-acting somatostatin analog controls acid and gastrin secretion in benign, not in malignant, Zollinger-Ellison syndrome. 230 79

A 41-year-old woman with metastatic glucagonoma and the characteristic disabling rash, necrolytic migratory erythema, was treated with a synthetic somatostatin analog while waiting to undergo curative surgical resection. Plasma glucagon concentration (1,500-3,300 pg/ml, normal less than 200) remained elevated during analog therapy as the rash cleared. Only with surgical resection (partial pancreatectomy and partial hepatectomy) did glucagon levels return to normal. The therapeutic benefit caused by the analog in this syndrome differs from that in other endocrine tumor syndromes such as pancreatic cholera, carcinoid, or gastrinoma where circulating levels of tumor-produced agents are suppressed in conjunction with control of symptoms.
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PMID:Somatostatin analog-induced remission of necrolytic migratory erythema without changes in plasma glucagon concentration. 288 3

Twelve islet cell tumors and one islet cell hyperplasia were studied with immunocytochemical and radioimmunoassay methods. With immunocytochemical staining, all six insulinomas, one mixed insulinoma-glucagonoma, and four gastrinomas were positive for insulin, insulin and glucagon, and gastrin, respectively. Pancreatic polypeptide (PP) was positive in three insulinomas and one mixed insulinoma-glucagonoma. All of the tumors were positive for neuron-specific enolase (NSE). Radioimmunoassays of tissue extracts further disclosed that all functioning tumors contained more than one pancreatic hormone. PP concentrations of two insulinomas and one mixed insulinoma-glucagonoma were higher than that of normal control pancreases. A study of protein meal-stimulated PP secretion revealed that three of the insulinoma cases and two gastrinoma cases exhibited higher plasma PP levels than the age-matched controls. The findings suggest that: both functioning and nonfunctioning islet cell tumors derive from neuroendocrine cells positive for NSE; all functioning islet cell tumors appear to contain PP in the tumor tissue as a minor component; as many as 70% of the patients with islet cell tumors present with abnormally higher plasma PP levels after protein meals; and a study of meal-stimulated PP secretion may well be used as a marker for the presence of functional islet cell tumors.
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PMID:Pancreatic polypeptide in islet cell tumors. Morphologic and functional correlations. 299 43

We have studied the concentration of various gastrointestinal peptides in a crude porcine secretin (Boots) preparation and pure natural porcine secretin (GIH, Kabi) preparation. Boots secretin was found to contain 140.3 ng secretin, 1.27 ng human pancreatic polypeptide (hPP), 1.03 ng gastrin, 137.4 ng cholecystokinin (CCK), 241 microU insulin, 1.86 ng vasoactive intestinal polypeptide (VIP), 2.22 ng glucagon and 6.60 ng somatostatin (SRIF) per Crick Harper unit Boots secretin. Sephadex gel filtration demonstrated that the immunoreactivity was due to the hormone per se. GIH secretin contained 240 ng secretin per clinical unit (CU) and less than detectable concentrations of hPP, gastrin, CCK, insulin, VIP, glucagon and SRIF. To determine the clinical significance of having contaminating peptides in Boots secretin, we investigated the effect(s) in 4 subjects. Determined in a highly gastrin-specific assay, the mean plasma gastrin response to Boots secretin administration was slightly, but not significantly greater than the GIH secretin response at 1 and 2.5 minutes. However, in some subjects false positive elevations in plasma gastrin immunoreactivity occurred when some commercially available kit gastrin assays were employed. After intravenous injection of Boots secretin, mean plasma hPP levels rose significantly more than after GIH secretin administration. The mean peak plasma insulin level after GIH secretin administration was significantly higher than after Boots secretin. Neither secretin preparation caused a change in plasma glucose, glucagon and SRIF levels. From these results, it is suggested that GIH secretin be used as the preparation of choice in provocative testing for diagnosing gastrinoma or deficiencies of exocrine pancreatic function.
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PMID:Stimulation of human pancreatic polypeptide and gastrin by Boots and GIH secretin: in vitro and in vivo studies. 355 22

Prospective screening was carried out in 12 members of three families with multiple endocrine adenopathies, type I (MEA,I) and in 14 patients with no multiple endocrine adenopathies with and without other endorcinopathies. Elevated basal and responsive (after a meal) plasma concentrations of a relatively new candidate-hormone, human pancreatic polypeptide (hPP), were associated with pancreatic apudoma tumors in three asymptomatic patients with multiple endocrine adenopathies, type I. Two of these patients had excision of the tumors that resulted in normal plasma hPP concentrations postoperatively. Both tumors contained hPP predominantly by immunocytochemistry; one, a pure pancreatic polypeptide apudoma, was studied extensively demonstrating also by radioimmunoassay a high content of hPP and negligible amounts of insulin, glucagon, somatostatin, vasoactive intestinal polypeptide and gastrin. In this patient plasma concentrations of other polypeptides including insulin, glucagon, somatostatin, vasoactive intestinal polypeptide, gastrin, parathyrin, thyrocalcitonin, prolactin, corticotropin, growth hormone, thyrtropin and amine, serotonin, were within normal limits. The other patient, after excision of an hPP-detected pancreatic mixed hPP-gastrinoma, also became eugastrinemic postoperatively. Normal basal plasma hPP concentrations, but with exaggerated hPP responses to a meal in 11 patients, were associated with various combinations of islet cell hyperplasia, antral G cell hyperplasia with moderate hypergastrinemia and parathyroid hyperplasia. The patients with multiple endocrine adenopathies who have demonstrated this type of increased hPP response to a meal have not been operated on but are at risk for islet hyperplasia. Four of the 12 patients with multiple endocrine adenopathies, type I, with both normal basal and normally responsive hPP concentrations have no evidence as yet of pancreatic involvement.
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PMID:Pancreatic polypeptide as screening marker for pancreatic polypeptide apudomas in multiple endocrinopathies. 624 7


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