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)

Multiple endocrine neoplasia type 1 (MENI) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline MEN1 mutations have been identified in most MEN1 families. Germline MENI mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MENI gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies. MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as cyclin D1 and P53) has been found, but much less frequently than MEN1 mutation. The majority of germline and somatic MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin's metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy.
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PMID:The gene for multiple endocrine neoplasia type 1: recent findings. 1042 35

Neuroendocrine tumours are seen on arteriography as diffusely enhancing masses without tumour vessels and without arteriovenous shunting. In 70 patients with surgically proven tumours, the sensitivity of angiography was 68% for extrapancreatic and 86% for hepatic lesions. Hepatic metastases have always been easier to demonstrate arteriographically than the primary tumour because of the absence of overlying bowel. Portal venous sampling is a sensitive technique for detecting functioning gastroenteropancreatic tumours. Sampling the small veins about the pancreatic head yielded a sensitivity of 62% but this is an invasive procedure in which considerable experience is required. Intra-arterial secretagogue, secretin for gastrinomas and calcium for insulinomas, selectively injected into the pancreatic and the hepatic arteries produce a diagnostic gastrin or insulin gradient respectively. The localization sensitivity of arterial stimulation with venous sampling is 77-89% for gastrinoma and 92% for pancreatic insulinoma. Recently, spiral CT in conjunction with selective intra-arterial rather than intravenous injection of contrast may increase the detection sensitivity of duodenal and pancreatic gastrinomas.
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PMID:Localization of gastroenteropancreatic tumours by angiography. 1060 23

The neuropeptide gastrin releasing peptide (GRP) stimulates insulin secretion and induces oscillations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](cyt)) in clonal insulinoma cells. It is not known whether GRP affects [Ca(2+)](cyt) in normal beta cells. We investigated, in single, normal, mouse islet beta cells, the effects of GRP on [Ca(2+)](cyt), by dual wavelength spectrophotofluorometry. Beta cells were identified by their typical response to glucose or tolbutamide. At 15 mM glucose, GRP (100 nM) evoked an immediate [Ca(2+)](cyt) transient to 423 +/- 48 nM compared to 126 +/- 18 nM before GRP (P < 0.001). After the initial transient, [Ca(2+)](cyt) exhibited either a sustained elevation or oscillations. At 3.3 mM glucose, in cells with a non-oscillating [Ca(2+)](cyt), GRP stimulated a prompt increase in [Ca(2+)](cyt) (from 60 +/- 6 to 285 +/- 30 nM, P = 0.024) followed by either a sustained increase in [Ca(2+)](cyt) or [Ca(2+)](cyt) oscillations. We conclude that GRP promptly elevates [Ca(2+)](cyt) by a direct action in normal mouse pancreatic beta cells.
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PMID:Direct cytoplasmic CA(2+) responses to gastrin-releasing peptide in single beta cells. 1116 63

The major phenotypes of multiple endocrine neoplasia type 1 (MEN 1) consist of three lesions characterized by hyperparathyroidism, pituitary tumors, and endocrine pancreatic tumors. The endocrine pancreatic tumors are a significant cause of disease-related mortality in MEN 1. Although symptomatic pancreatic tumors such as insulinoma and gastrinoma should be resected, the management of asymptomatic pancreatic tumors is not established. In asymptomatic pancreatic tumors, the most important factor is the propensity for malignant transformation of the tumors. Although there are no means to foresee it, the size of the pancreatic tumors might be predictive of malignant development in MEN 1. We report here a patient with MEN 1 who had a large asymptomatic pancreatic tumor. The patient (72-yr-old man) was diagnosed with primary hyperparathyroidism and underwent a total parathyroidectomy. Genetic examination showed a germline mutation of the MEN1 gene (E45G). Abdominal magnetic resonance imaging revealed a large (>6 cm) tumor with a heterogeneous pattern in the tail of the pancreas. No metastases of the tumor were evident. Serum levels of insulin, gastrin, and glucagon were normal, and the patient had no symptoms. Operative resection was performed, and microscopic examination revealed that the tumor was an islet cell tumor stained with multiple hormones. This is a case indicating that asymptomatic pancreatic tumors associated with MEN 1 might be indolent independent of their size.
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PMID:Large and asymptomatic pancreatic islet cell tumor in a patient with multiple endocrine neoplasia type 1. 1121 36

1. The acidic interior of neuroendocrine secretory vesicles provides both an energy gradient for amine-proton exchangers (VMATs) to concentrate small transmitter molecules, for example catecholamines, and an optimal pH for the prohormone convertases which cleave hormone precursors. There is evidence that VMAT activity modulates prohormone cleavage, but in the absence of measurements of pH in secretory vesicles in intact cells, it has not been possible to establish whether these effects are attributable to raised intravesicular pH due to proton transport through VMATs. 2. Clones were generated of the hamster insulinoma cell line HIT-T15 expressing a pH-sensitive form of green fluorescent protein (GFP-F64L/S65T) targeted to secretory vesicles, with and without co-expression of VMAT2. In order to study prohormone cleavage, further clones were generated that expressed preprogastrin with and without co-expression of VMAT2. 3. Confocal microscopy of GFP fluorescence indicated that the pH in the secretory vesicles was 5.6 in control cells, compared with 6.6 in cells expressing VMAT2; the latter was reduced to 5.8 by the VMAT inhibitor reserpine. 4. Using a pulse-chase labelling protocol, cleavage of 34-residue gastrin (G34) was found to be inhibited by co-expression with VMAT2, and this was reversed by reserpine. Similar effects on vesicle pH and G34 cleavage were produced by ammonium chloride. 5. We conclude that VMAT expression confers the linked abilities to store biogenic amines and modulate secretory vesicle pH over a range influencing prohormone cleavage and therefore determining the identity of regulatory peptide secretory products.
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PMID:Measurement of secretory vesicle pH reveals intravesicular alkalinization by vesicular monoamine transporter type 2 resulting in inhibition of prohormone cleavage. 1125 Oct 39

We report a patient with insulinoma associated with Zollinger-Ellison syndrome. A 67-year-old woman was first admitted to our hospital for an abdominal mass. Abdominal computed tomography (CT) revealed a large pancreatic tumor, which was then diagnosed as an unresectable pancreatic adenocarcinoma. At the age of 71, she presented symptoms of hypoglycemia. Fasting blood glucose was 21 mg/dl and plasma immunoreactive insulin level was 846 microU/ ml. Plasma gastrin, glucagon, vasoactive intestinal polypeptide and somatostatin levels were all normal. At the age of 73, hypoglycemic attacks occurred more frequently and she was admitted to our hospital. Abdominal CT scan showed multiple liver metastases. Chemotherapy with 5-fluorouracil and doxorubicin was performed. Three months later, she had an emergency laparotomy because of a perforated duodenal ulcer. Plasma gastrin level was 1,960 pg/ml at that time. Gastric hypersecretion was well controlled with a proton pump inhibitor (lansoprazole) but she died of widespread cancer dissemination 8 years after her first admission. On autopsy, histologic examination revealed a mixed acinar-endocrine carcinoma of the pancreas. Immunohistochemical stains were positive for insulin, gastrin, and alpha1-antitrypsin.
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PMID:Insulinoma with subsequent association of Zollinger-Ellison syndrome. 1139 7

Gastroenteropancreatic (GEP) neoplasms originate from any of the various cell types belonging to the neuroendocrine system. A general characteristic of GEP endocrine tumours is that the vast majority produce and secrete a multitude of peptide hormones and amines. Many patients with malignant metastasising tumours present clinical symptoms related to hormone hyperproduction. These include the so-called carcinoid syndrome, characterised by flushing, diarrhoea, wheezing and right heart disease, which is predominantly associated with the serotonin- and tachykinins-producing carcinoids of the midgut. Several types of syndrome associated with GEP endocrine tumors are caused by overproduction of a specific hormone. For instance, the well-known Zollinger-Ellison syndrome is gastrin-mediated. The so-called 'insulinoma syndrome' depends on excessive production of insulin and proinsulin, resulting in hypoglycemia. The 'glucagonoma syndrome' is characterised by necrolytic migratory erythema, diabetes and diarrhoea. The Verner-Morrison syndrome, which is brought about by high circulating levels of vasointestinal peptide (VIP). produces severe secretory diarrhoea. Finally the 'somatostatinoma syndrome' involves gallbladder dysfunction and gallstones, diarrhoea with or without steatorrhea, and impaired glucose tolerance. The biochemical diagnosis of endocrine digestive tumors is based on general and specific markers. The best general markers are chromogranin A (CgA) and pancreatic polypeptide (PP). Specific markers for endocrine tumors include insulin, gastrin, glucagon, vaso intestinal polypeptide (VIP), somatostatin and the primary cathabolic product of serotonin, 5-hydroxyndoleacetic acid (5-HIAA). Localisation procedures commonly applied, in the diagnosis of endocrine tumours include ultrasound (US), computed tomography (CT) and somatostatin receptor scintigraphy (SRS).
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PMID:Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. 1176 60

About 25% of patients with ZES have MEN 1. Except diarrhoea, less frequent in patients with ZES-MEN 1 than in sporadic ZES, and specific MEN 1-related signs, clinical characteristics are similar in both ZES types. Acid output and gastrin levels are also similar whether in the basal state or after secretin stimulation. Primary hyperparathyroidism (PHPT) exists in the majority of ZES-MEN 1 patients, 30% have pituitary adenoma (prolactinomas for half), 30% adrenal involvement, 25 to 30% have EC-Lomas; bronchial and thymic carcinoids have probably been underevaluated. Gastrinomas are multiple predominantly located in the duodenal wall, but also in the pancreas in association with clinically silent endocrine tumors. The spread of the disease: metastases to the liver (LM), mediastinum, bones, is evaluated at best by Octreoscan. Endoscopic ultrasonography evaluates the number, size and anatomical characteristics of gastrinomas. Patients without LM have an excellent prognosis. Surgery never cures ZES, but is necessary in case of associated life-threatening condition such as insulinoma and has been advocated to prevent LM development in patients with large pancreatic tumor(s). However although, indeed, the size of the tumor, when located in the pancreas > 3 cm, favours metachronous LM occurrence, surgery, in our experience, has not been able to prevent LM development. Hepatic malignancies remain however the most pejorative prognostic determinant for survival and raise the most difficult therapeutic challenge. Surgery is the best option whenever feasible; specific chemotherapy and chemo-embolisation have not conclusively achieved definite successes. Long-term octreotide treatment, however, has been shown recently to obtain tumour stabilisation. Internal irradiation with 90 Ytrium-labelled octreotide is a new promising option, presently under evaluation (Novartis European trial). Preliminary results are promising.
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PMID:[Diagnostic and therapeutic strategies in Zollinger-Ellison syndrome associated with multiple endocrine neoplasia type I (MEN-I): experience of the Zollinger-Ellison Syndrome Research Group: Bichat 1958-1999]. 1514 2

Over the last decade somatostatin receptor scintigraphy using various derivatives of long-acting somatostatin analogues has gained its place in the management of pancreatic islet-cell tumours. Scintigraphy is based on the high-affinity binding of such somatostatin analogues to receptors over-expressed by these tumour types. Following the introduction of (111)In-DTPA-D-Phe(1)-octreotide, clinical studies with radiolabelled DOTA-Tyr(3)-octreotide and DOTA-Tyr(3)-octreotate derivatives have shown considerable improvement of imaging results with increased tumour uptake. One of the newer developments, (68)Ga-labelled DOTA-Tyr(3)-octreotide, has shown promising results in patients with pancreatic islet-cell tumours, based on the high-affinity binding to the somatostatin receptor subtype 2 in combination with positron emission tomography (PET) technology. Other peptides--such as ligands for the gastrin/CCK2 receptors or vasoactive intestinal peptide (VIP)--have also been studied for imaging pancreatic cell tumours. Whereas small-sized gastrinoma, somatostatinoma, glucagonoma, carcinoid and VIPoma are frequently detected by somatostatin receptor scintigraphy, insulinoma may escape detection due to reduced receptor expression. Following peptide receptor scintigraphy, a change in patient management is reported in up to 30% of patients. When labelled with (90)Y or (177)Lu, some somatostatin analogues have been applied to patients in advanced stages of the disease. Despite positive response data in 50% of patients, long-term results and survival rates are lacking.
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PMID:Nuclear medicine in the detection and management of pancreatic islet-cell tumours. 1576 96

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET. GRS was directly compared with SRS. If lesions were visible on GRS but not detectable by SRS, other imaging modalities (MRI, CT) and follow-up were used for verification. Of the 60 evaluable patients, 51 had carcinoid tumours, 3 gastrinomas, 2 glucagonomas, 1 insulinoma and 3 paragangliomas. The overall tumour-detection rate was 73.7% for GRS and 82.1% for SRS. In the 11 patients with negative SRS, GRS was positive in 6 (54.5%). Based on the number of tumour sites detected and the degree of uptake, GRS performed better than SRS in 13 patients (21.7%), equivalent images were obtained in 18 cases (30.0%) and SRS performed better in 24 (40.0%) cases. In six of the SRS positive patients, 18 additional sites of tumour involvement could be detected. Overall, GRS detected additional tumour sites in 20% of the patients. Localisation of the primary tumours or their functional status had no influence on the outcome of imaging. GRS should be performed in selected patients as it may provide additional information in patients with NET with equivocal or absent somatostatin uptake.
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PMID:Added value of gastrin receptor scintigraphy in comparison to somatostatin receptor scintigraphy in patients with carcinoids and other neuroendocrine tumours. 1715 65


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