Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study relating to gastrin release from gastrinoma cells by neuromedin B and C-terminal decapeptide of gastrin releasing peptide (GRP-10) has not yet been reported. Therefore, we studied the effects of neuromedin B and GRP-10 on gastrin release from cultured dispersed cells prepared from both the primary tumor in the pancreas and the metastatic tumor in the liver from a case of malignant Zollinger-Ellison syndrome. Both the primary and metastatic tumors obtained by a curative operation contained similar concentrations of gastrin and glucagon, whereas the primary tumor contained 10 times more insulin than the metastatic tumor. Gastrin release from cultured cells of both tumors was suppressed by 0.1 and 10 nM neuromedin B and tended to be suppressed by 0.1-10 nM GRP-10. However, insulin release from cultured cells of the pancreatic tumor was stimulated by GRP-10, but not by neuromedin B. These results might suggest that receptor function for the bombesin family peptides is abnormal in gastrinoma cells in both primary and metastatic tumors, and that a major source of insulin secretary cells is the contaminated normal islet cells in the primary tumor.
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PMID:Effects of neuromedin B and GRP-10 on gastrin and insulin release from cultured tumor cells of a malignant gastrinoma. 210 91

The mechanism for secretin-induced gastrin release in the Zollinger-Ellison syndrome is uncertain. We evaluated whether the stimulatory effect of intravenous secretin on gastrin release was partly mediated through a beta-adrenergic stimulatory mechanism. Serum gastrin concentrations and heart rate were monitored in six patients with the Zollinger-Ellison syndrome. Secretin (2 clinical units/kg) increased mean serum gastrin concentrations from 1558 pg/ml basally to a peak of 3683 pg/ml (136% above baseline). This increase was not altered by pretreatment with 2 mg of propranolol intravenously, a dose which in previous studies blocked terbutaline-induced gastrin release. Secretin increased heart rate by 14 beats/min (20% above base-line) and this also was not altered by propranolol pretreatment. Thus, the stimulatory effects of secretin on gastrinoma cells and the heart do not appear to be mediated by beta-adrenergic receptors.
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PMID:Effect of propranolol on secretin-induced gastrin release and secretin-induced tachycardia in patients with the Zollinger-Ellison syndrome. 210 52

The effect of epinephrine on the plasma gastrin level was investigated in three patients with Zollinger-Ellison syndrome (ZES) and in 14 normal subjects. Two ZES patients had undergone total gastrectomy, and the third had undergone subtotal gastrectomy before our study. A significant increase in plasma gastrin, from 23 +/- 5 pg/ml to 53 +/- 20 pg/ml, in response to intravenous epinephrine (40 ng/kg.min), was observed in the normal subjects. This response was completely abolished by beta-blockade. In the ZES patients, epinephrine (40 ng/kg.min) also resulted in an increase in the plasma concentration of gastrin. The basal and maximum concentrations of gastrin were 580 and 1680 pg/ml in patient 1, 145000 and 320000 pg/ml in patient 2, and 200 and 1800 pg/ml in patient 3, respectively. beta-Adrenergic blockade suppressed the epinephrine-stimulated gastrin release in these patients as well. Graded intravenous doses of epinephrine given to the ZES patients resulted in elevation of the plasma gastrin in a dose-dependent manner. Insulin hypoglycemia caused an increase in both plasma epinephrine and plasma gastrin in ZES patients and normal subjects. A significant correlation between plasma gastrin and epinephrine during insulin hypoglycemia was observed in both groups. Exercise, with use of a bicycle ergometer, resulted in an increase in plasma epinephrine. An increase in plasma gastrin with exercise was observed in the ZES patients, and this was also suppressed by beta-blockade. The results suggest that gastrinoma cells, like normal G cells, are equipped with beta-adrenergic receptors that regulate gastrin release.
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PMID:Beta-adrenergic regulation of gastrin release from gastrinoma cells. 215 79

In two patients with malignant gastrinoma and the Zollinger-Ellison syndrome, we were able to use selective arterial stimulation with secretin as a technique to localize the lesions accurately, allowing resection. The technique of selected arterial secretin stimulation is one of measuring variations in gastrin levels in both the hepatic vein and a peripheral artery at specified times after injection of secretin into a specific artery. When the criteria for localization have been met, one can plot the presence of the gastrinoma within the blood supply of the injected artery and, using angiograms, thus accurately localize the lesion. This method promises to be a valuable additional tumor-localizing procedure, particularly when gastrinomas are extrapancreatic.
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PMID:Selective arterial stimulation of secretin in localization of gastrinomas. 216 70

The effect of an octapeptide analogue of somatostatin, octreotide, on tumor blood flow was evaluated with angiography in eight patients with hepatic endocrine tumors; one patient had primary intrahepatic gastrinoma, two patients had hepatic metastases from gastrinomas, two patients had VIPomas (vasoactive intestinal polypeptide-secreting tumor), and three patients had carcinoid tumors. Octreotide caused a marked decrease in tumor blood flow in two patients with gastrinomas and two with VIPomas. One patient could not be evaluated due to the lack of a tumor blush on a control angiogram. In patients with carcinoid tumors, octreotide caused a slight reduction in blood flow through the tumors in two patients, while there was no change in one patient. Octreotide markedly decreased gastrin and gastric acid secretion in two of three patients with gastrinomas, lowered VIP and stopped the diarrhea in patients with VIPomas, and controlled symptoms in two of three patients with carcinoid tumors. The vasoactive effect of octreotide on hepatic endocrine tumors may be a direct action on tumor blood supply or secondary to inhibition of the endocrine tumor cell secretion and consequent decreased blood flow.
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PMID:Effect of somatostatin analogue (octreotide) on blood flow to endocrine tumors metastatic to the liver: angiographic evaluation. 217 Oct 15

Islet cell carcinoma frequently produces more than one chemical product, although its clinical expression is usually restricted to a single hormone. We describe an unusual patient who presented with full-blown metastasizing gastrinoma. He was treated with cimetidine for five years and then streptozotocin therapy, which resulted in a regression in hepatomegaly and a fall in serum gastrin levels. Following one year's therapy with streptozotocin, he was admitted in hyperinsulinemic hypoglycemic stupor. This appears to be the first reported case of a "shift" from clinical gastrinoma to insulinoma possibly related to prolonged streptozotocin therapy.
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PMID:Insulinoma after streptozotocin therapy for metastatic gastrinoma: natural history or iatrogenic complication? 217 60

Because of increasingly effective oral antisecretory agents, gastric acid hypersecretion is now able to be controlled in all patients with Zollinger-Ellison syndrome with the result that the natural history of the gastrinoma is becoming the major determinant of long-term survival. In this article recent advances in the management of the gastrinoma itself are reviewed, including results with new modalities such as intraoperative ultrasound, MRI, and selective gastrin sampling to localize gastrinoma in patients with Zollinger-Ellison syndrome, as well as recent results of the treatment of metastatic and localized gastrinomas.
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PMID:Zollinger-Ellison syndrome. Recent advances in the management of the gastrinoma. 218 29

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

Processing-independent radioimmunoanalysis for progastrin showed that extracts of normal pancreatic tissue from normal subjects (n = 5) and from patients with adenocarcinoma of the papilla of Vater (n = 4) contain progastrin and its products. The concentrations varied from 0.1 to 5.8 pmol/g tissue, of which carboxyamidated bioactive gastrins constituted 0.03-1.9 pmol/g. In histologically normal and nonneoplastic pancreatic tissue from patients with duodenal (n = 3) and pancreatic (n = 2) gastrinomas the expression of gastrin was significantly higher-14.5 pmol/g (median), of which 28% was bioactive amidated gastrins. Gastrin-17 was the main bioactive product, but its immediate precursor, glycine-extended gastrin-17, constituted the predominant part of the preprogastrin product in pancreatic tissue. Proper gastrinoma tissue contained several precursor forms, including intact unprocessed progastrin. Progastrins were also found in high concentrations in plasma from the gastrinoma patients. The results raise the possibility that increased expression of progastrin and its products in non-neoplastic pancreatic tissue is a primary defect predisposing to neoplasia.
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PMID:Gastrin in non-neoplastic pancreatic tissue from patients with and without gastrinomas. 221 98

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


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