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)

The gastric hormone gastrin stimulates gastric acid secretion and epithelial cell proliferation. Multiple active products are generated from the precursor, preprogastrin, including the well-characterized amidated gastrins acting at the cholecystokinin-2 (CCK-2, or gastrin-CCK(B)) receptor, and others that may be growth factors in a range of cancers. Plasma concentrations of the amidated gastrins are elevated as a consequence of gastrin-secreting tumours (gastrinomas) and in conditions in which the normal inhibition of the antral G-cell by acid is depressed, for example chronic atrophic gastritis and prolonged treatment with proton pump inhibitors. There may also be increased gastrin release in Helicobacter pylori infection. Provocative tests for the diagnosis of gastrinoma include the secretin and calcium infusion tests. Hypergastrinaemia is associated with enterochromaffin-like (ECL) cell proliferation; the factors that determine progression to ECL cell dysplasia and gastric ECL cell carcinoid tumours are discussed. Several strategies for inhibiting the effects of gastrin are under evaluation, and their potential application is discussed.
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PMID:Clinical endocrinology and metabolism. Gastrin. 1553 75

Recently we have reported synergistic effects between glycine-extended gastrin (G-gly) and amidated gastrin-17 on acid secretion in short-term infusion studies. In the present study, we examined the long-term effect of G-gly on the atrophy-promoting effects of amidated gastrin in the mouse stomach with or without Helicobacter infection. Transgenic mice overexpressing amidated gastrin (INS-GAS mice), G-gly (MTI/G-gly mice), and both peptides (INS-GAS/G-gly mice) were used for assessment of acid secretion and ulcer susceptibility and histologic examination and scoring of preneoplastic lesions in response to the 3 and 6 months Helicobacter felis (H. felis) infection. We found that MTI/G-gly mice had normal gastric histology and acid secretion. Double transgenic (INS-GAS/G-gly) mice showed 2-fold increases in acid secretion compared with INS-GAS mice. Acute peptic ulcers after pyloric ligation were noted in 50% of the INS-GAS/G-gly mice but in none of the INS-GAS mice at 6 months of age. Whereas male INS-GAS mice had a >50% decrease in the numbers of parietal cell and enterochromaffin-like cell at 6 months of age, the male double transgenic mice had no such decrease. Overexpression of G-gly reduced the scores of preneoplasia in the stomach; however, it did not prevent the development of amidated gastrin-dependent gastric cancer in both H. felis-infected mice and uninfected mice. We conclude that G-gly synergizes with amidated gastrin to stimulate acid secretion and inhibits parietal cell loss in INS-GAS/G-gly mice. The overexpression of G-gly seems to increase the susceptibility to peptic ulcer disease and delay the development of Helicobacter-mediated gastric preneoplasia in this model.
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PMID:Overexpression of glycine-extended gastrin inhibits parietal cell loss and atrophy in the mouse stomach. 1554 80

Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 +/- 15 years versus 62 +/- 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 +/- 9 to 95 +/- 16 fl, serum ferritin levels from 4 +/- 2 to 37 +/- 41 microg/L, gastrin level from 166 +/- 118 to 382 +/- 299 pM/L (349 +/- 247 to 800 +/- 627 pg/mL), and a decrease in cobalamin level from 392 +/- 179 to 108 +/- 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.
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PMID:Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. 1700 59

We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were determined in the plasma of 87 blood culture-confirmed typhoid fever cases (collected after clinical recovery) and 232 random healthy controls without a history of typhoid fever, in the Jatinegara district, Jakarta. Patients with typhoid fever more often than controls were seropositive for H. pylori IgG (67% vs. 50%, P<0.008), when antibody titres were dichotomized around median titres observed in controls. H. pylori IgA seropositivity was not associated with typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e. gastrin > or =25 or > or =100 ng/l) were not significantly elevated in typhoid fever cases compared to controls (P=0.54 and P=0.27 respectively). In a multivariate analysis, typhoid fever was independently associated with young age (<33 years, median age of the controls) [odds ratio (OR) 7.93, 95% confidence interval (CI) 3.90-16.10], and H. pylori IgG seropositivity (OR 1.93, 95% CI 1.10-3.40). Typhoid fever was independently associated with H. pylori IgG seropositivity, but not with elevated gastrin concentration. Therefore, the association suggests a common risk of environmental exposure to both bacteria, e.g. poor hygiene, rather than a causal relationship via reduced gastric acid production.
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PMID:Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia. 1640 64

We attempted to clarify the pathogenesis of gastric inflammation in the cardia. Eighty Japanese participated in this study. Biopsy specimens of the gastric antrum, corpus, and cardia (1 cm from the squamocolumnar junction) were obtained, and histological gastritis was evaluated. Cardiac inflammation was also evaluated using magnifying gastroscopy. We examined Helicobacter pylori infection, gastric juice pH/bile acid (BA), serum pepsinogen and gastrin levels, gastroesophageal reflux disease (GERD), and habitual smoking and assessed the relations between these factors and cardiac inflammation. The prevalence of H. pylori infection was statistically higher in patients with cardiac inflammation than in those without inflammation (P < 0.05). The relationship was also demonstrated by magnifying gastroscopy. Cardiac inflammation was linked to low acid output but not linked to the BA concentration or habitual smoking. Cardiac inflammation was more pronounced in patients without GERD. These results suggest that H. pylori is a major risk factor for cardiac inflammation in the Japanese.
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PMID:Helicobacter pylori infection is the major risk factor for gastric inflammation in the cardia. 1660 36

Intestinal metaplasia has been investigated extensively as a possible premalignant condition for stomach cancer but its pathogenesis is still not fully understood. In the present study, we examined the relationship between endocrine and mucous cell marker expression periodically after Helicobacter pylori infection in the Mongolian gerbil model. The numbers of chromogranin A (CgA)-positive, gastrin-positive and gastric inhibitory polypeptide (GIP)-positive cells in H. pylori-infected groups was increased significantly compared with the non-infected case. However, CgA-positive and gastrin-positive cells then decreased from 50 through 100 experimental weeks after H. pylori infection, whereas GIP-positive cells increased. Coexistence of gastrin-positive and GIP-positive cells was detected in the same gastric and intestinal mixed phenotypic glandular-type glands. In conclusion, the endocrine cell phenotype is in line with that of the mucous counterpart in the glands of H. pylori-infected Mongolian gerbil stomach, supporting the concept that development of intestinal metaplasia is due to the abnormal differentiation of a stem cell.
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PMID:Helicobacter pylori infection stimulates intestinalization of endocrine cells in glandular stomach of Mongolian gerbils. 1698 75

The assessment of fasting serum gastrin (FSG) is essential for the diagnosis and management of patients with the Zollinger-Ellison syndrome (ZES). Although many studies have analyzed FSG levels in patients with gastrinoma, limited information has resulted from these studies because of their small size, different methodologies, and lack of correlations of FSG levels with clinical, laboratory, or tumor features in ZES patients. To address this issue, we report the results of a prospective National Institutes of Health (NIH) study of 309 patients with ZES and compare our results with those of 2229 ZES patients in 513 small series and case reports in the literature. In the NIH and literature ZES patients, normal FSG values were uncommon (0.3%-3%), as were very high FSG levels >100-fold normal (4.9%-9%). Two-thirds of gastrinoma patients had FSG values <10-fold normal that overlap with gastrin levels seen in more common conditions, like Helicobacter pylori infection or antral G-cell hyperplasia/hyperfunction. In these patients, FSG levels are not diagnostic of ZES, and gastrin provocative tests are needed to establish the diagnosis. Most clinical variables (multiple endocrine neoplasia type 1 status, presence or absence of the most common symptoms, prior medical treatment) are not correlated with FSG levels, while a good correlation of FSG values was found with other clinical features (prior gastric surgery, diarrhea, duration from onset to diagnosis). Increasing basal acid output, but not maximal acid output correlated closely with increasing FSG. Numerous tumoral features correlated with the magnitude of FSG in our study, including tumor location (pancreatic > duodenal), primary size (larger > smaller) and extent (liver metastases > local disease). In conclusion, this detailed analysis of FSG in a large number of patients with ZES allowed us to identify important clinical guidelines that should contribute to improved diagnosis and management of patients with ZES.
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PMID:Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature. 1710 78

Many studies have pointed out a possible role of gut peptides, including gastrin and ghrelin, in the pathogenesis and natural history of gastrointestinal malignancies, one of the most common death cause in the Western world. The objective of this work is to check gastrin and ghrelin serum levels in patients with colorectal cancer according to tumour's location, stage, Helicobacter pylori infection and BMI, in order to understand the two peptides' behaviour through the tumour's natural history and evaluate their assay's use in research and clinical practice. Twenty-nine subjects affected by colorectal cancer and 50 healthy controls were studied. Circulating gastrin and ghrelin levels and H. pylori serum antibodies were assessed by radioimmunologic assay and ELISA method. Gastrin and ghrelin serum levels were respectively slightly higher and significantly lower in colon cancer patients than in controls. Gastrin levels were higher in patients carrying left colon cancer and H. pylori infection while ghrelin levels were lower in both these groups. Both hormones' serum levels decreased from tumour earlier to later stages. Significant differences persisted in the correlation between BMI and ghrelin levels in controls but not in patients. Additional studies are necessary to ascertain the significance of gastrin and ghrelin opposite behaviour in colon cancer probably linked with interferences in endocrine pathways involving other gut peptides in this compromised condition.
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PMID:Circulating gastrin and ghrelin levels in patients with colorectal cancer: correlation with tumour stage, Helicobacter pylori infection and BMI. 1725 85

Long-term use of proton pump inhibitors (PPIs) has been reported to worsen corpus atrophic gastritis in patients with Helicobacter pylori infection. On the other hand, PPIs have been associated with fundic gland-type gastric polyps and various histological changes. In the present study, we attempted to establish a protocol for omeprazole (OPZ) administration to rats over a longer period and examined the morphological changes in the gastric mucosa after administration of OPZ for 6 months. A total of 34 Wistar rats (8 weeks old) were used. In a preliminary experiment to determine the appropriate dose of OPZ, the rats had ad libitum access to food containing different doses of OPZ for 1 month. We found an approximate dose of 100 mg/kg body weight/day of OPZ to be most suitable from the point of view of intragastric pH, body weight, and serum gastrin level. In the experiment proper, rats were divided into two groups, either control or OPZ diets, and morphological changes in the gastric mucosa in each group were then examined by hematoxylin and eosin and immunohistochemical staining with alpha-amylase, trypsin, and chromogranin A. Multiple vacuolar degeneration of parietal cells and numerous small mucous cells were evident at 1 month after treatment with OPZ. At 6 months after treatment with OPZ, cystic degeneration and acinar-cell-like cells containing red granules positive for alpha-amylase and trypsin and negative for chromogranin A were detected in the OPZ rats. The serum gastrin level in the OPZ group was significantly higher than that in the control group. We have established a protocol for long-term administration of OPZ in rats that is a useful model for analyzing morphological changes after long-term PPI therapy. Long-term OPZ treatment causes hypergastrinemia and pancreatic acinar cell metaplasia in this animal model.
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PMID:Development of pancreatic acinar cell metaplasia after successful administration of omeprazole for 6 months in rats. 1735 42

The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin.
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PMID:Attack and defence in the gastric epithelium - a delicate balance. 1741 51


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