gastrins and Intestinal-Diseases

Gastrin and gastrin receptor-deficient mice have been used for genetic dissection of the role of gastrins in maintaining gastric homeostasis and control of acid secretion. The gastrin knockout mice are achlorhydric due to inactivation of the ECL and parietal cells. Moreover, this achlorhydria is associated with intestinal metaplasia and bacterial overgrowth, which ultimately leads to the development of gastric tumours. The association between progastrin, progastrin-derived processing intermediates and colorectal carcinogenesis has also been examined through genetic or chemical cancer induction in several mouse models, although the clinical relevance of these studies remains unproven. While others have focused on models of increased gastrin production, the present review describes the lessons learned from gastrin-deficient mice. Study of these mice helps our understanding of how dysregulation of gastrin secretion may be implicated in human disease.

Topics: Achlorhydria; Animals; Gastric Acid; Gastric Mucosa; Gastrins; Gene Expression Regulation; Intestinal Diseases; Metaplasia; Mice; Mice, Knockout; Models, Biological; Receptor, Cholecystokinin B; Stomach Neoplasms

Topics: Animals; Biopsy; Cell Differentiation; Cell Division; Colonic Diseases; Culture Techniques; Digestive System; DNA; Epithelial Cells; Esophageal Diseases; Esophagus; Gastric Mucosa; Gastrins; Gene Expression Regulation; Genetic Markers; Humans; Intestinal Diseases; Intestine, Large; Intestine, Small; Neoplasm Transplantation; Oncogenes; Organ Culture Techniques; Stomach; Stomach Diseases

The lining of the intestinal tract is constantly renewed in a brisk but orderly fashion. Further acceleration of cell renewal is elicited by various stimuli, notably surgical shortening of the intestine and hyperphagia, which lead to prompt but persistent increases in mucosal mass. Progressive hypoplasia ensues when the small and large bowel are deprived of their normal contents, either by fasting (with or without parenteral nutrition) or by exclusion from intestinal continuity. All atrophic changes are reversed by refeeding or restoration of the normal anatomical disposition. Intestine responds to mucosal damage by regeneration from the crypts. Pancreatobiliary secretions mediate some of the tropic effects of chyme; systemic influences, both neurovascular and humoral, also play a part in the adaptive response of the gut.

Topics: Adaptation, Physiological; Adult; Animals; Cell Division; Colectomy; Colostomy; Female; Gastrins; Glucagon-Like Peptides; Humans; Hyperphagia; Hyperplasia; Hypertrophy; Ileum; Intestinal Diseases; Intestinal Mucosa; Intestines; Jejunum; Obesity; Parenteral Nutrition; Rats; Starvation

Topics: Adolescent; Adult; Aged; Child; Diagnosis, Differential; Diarrhea; Digestive System; Endocrine System Diseases; Female; Gastrectomy; Gastrins; Humans; Intestinal Diseases; Jejunum; Male; Middle Aged; Multiple Endocrine Neoplasia; Radiography; Recurrence; Zollinger-Ellison Syndrome

There is evidence that under various physiological circumstances long-term adaptation of structure and function of the gut occurs. The mechanisms of these changes are not clear but gastro-intestinal hormones may be involved. In particular, gastrin which has been shown experimentally to stimulate growth and development of parts of the gut, probably has a role in maintaining the structure of the normal upper alimentary tract. Cholecystokinin may be of major importance in producing adaptive changes in the pancreas in response to dietary modifications and enteroglucagon is possibly concerned with maintaining a normal small intestinal structure. The importance of the 'trophic' action of gatrointestinal hormones is becoming more widely recognised and as new gastro-intestinal hormones become established, this aspect of their physiological importance as well as their acute effects, will deserve attention.

Topics: Animals; Cholecystokinin; DNA; Duodenum; Female; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Diseases; Intestine, Small; Kidney Failure, Chronic; Lactation; Pancreas; Pregnancy; Rats; Secretin; Starvation; Weaning; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Antibodies; Aspirin; Feces; Galactosidases; gamma-Globulins; Gastric Juice; Gastrins; Gastrointestinal Diseases; Glutaminase; Humans; Intestinal Absorption; Intestinal Diseases; Intestines; Metabolism, Inborn Errors; Pancreatic Diseases; Pancreatitis; Radiography; Radionuclide Imaging; Triglycerides

Topics: Colon; Colon, Sigmoid; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Motility; Histamine; Humans; Injections, Intramuscular; Injections, Intravenous; Intestinal Diseases; Peptic Ulcer; Pylorus; Pyrazoles; Rectum; Stomach

Serum gastrin concentration can help diagnose gastrinomas in dogs if >3-10× the upper reference limit (URL), but antisecretory therapy and other conditions can also cause hypergastrinemia. Effects of antisecretory therapy (famotidine or ranitidine, omeprazole) on serum gastrin concentration in dogs with chronic enteropathy (CE) and its biological variation (BV) are unknown. Aim of the study was to evaluate serum gastrin in acid-suppressant-treated or -naïve CE dogs; test the association between serum gastrin and histopathologic findings in acid-suppressant-naïve CE dogs; and evaluate the BV of serum gastrin in dogs not receiving any gastric acid suppressive therapy. Samples from 231 dogs were used and serum gastrin was measured by chemiluminescence assay. Gastric and duodenal histologic lesions were evaluated and graded. BV of serum gastrin was evaluated in serial samples.. Antisecretory (particularly PPI) treatment leads to hypergastrinemia in CE dogs, but the concentrations seen in this study are unlikely to compromise a diagnosis of gastrinoma. Use of a population-based URL for canine serum gastrin and a URL of ≤27.8 ng/L are appropriate.

Topics: Animals; Biological Variation, Population; Dog Diseases; Dogs; Female; Gastrins; Helicobacter; Helicobacter Infections; Histamine H2 Antagonists; Intestinal Diseases; Male; Proton Pump Inhibitors; Stomach Diseases

Intestinal ischemia-reperfusion (I/R) injury is a devastating complication when the blood supply is reflowed in ischemic organs. Gastrin has critical function in regulating acid secretion, proliferation, and differentiation in the gastric mucosa. We aimed to determine whether gastrin has an effect on intestinal I/R damage. Intestinal I/R injury was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion, and the rats were induced to be hypergastrinemic by pretreated with omeprazole or directly injected with gastrin. Some hypergastrinemic rats were injected with cholecystokinin-2 (CCK-2) receptor antagonist prior to I/R operation. After the animal surgery, the intestine was collected for histological analysis. Isolated intestinal epithelial cells or crypts were harvested for RNA and protein analysis. CCK-2 receptor expression, intestinal mucosal damage, cell apoptosis, and apoptotic protein caspase-3 activity were measured. We found that high gastrin in serum significantly reduced intestinal hemorrhage, alleviated extensive epithelial disruption, decreased disintegration of lamina propria, downregulated myeloperoxidase activity, tumor necrosis factor-α, and caspase-3 activity, and lead to low mortality in response to I/R injury. On the contrary, CCK-2 receptor antagonist L365260 could markedly impair intestinal protection by gastrin on intestinal I/R. Severe edema of mucosal villi with severe intestinal crypt injury and numerous intestinal villi disintegrated were observed again in the hypergastrinemic rats with L365260. The survival in the hypergastrinemic rats after intestinal I/R injury was shortened by L365260. Finally, gastrin could remarkably upregulated intestinal CCK-2 receptor expression. Our data suggest that gastrin by omeprazole remarkably attenuated I/R induced intestinal injury by enhancing CCK-2 receptor expression and gastrin could be a potential mitigator for intestinal I/R damage in the clinical setting.

Topics: Animals; Benzodiazepinones; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gastrins; Intestinal Diseases; Male; Phenylurea Compounds; Porins; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptor, Cholecystokinin B; Reperfusion Injury

Topics: Acute Disease; Age Factors; Bacterial Infections; Calcium; Dysentery; Gastrins; Humans; Infant; Intestinal Diseases; Islets of Langerhans; Pancreas; Trypsin

The effects of the C-terminal tetrapeptide of gastrin, tetragastrin, on the colonic mucosa on Days 15 and 25 during intrarectal administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and its effects on the incidences of colonic tumors in experimental Wk 20 and 35 were investigated in Wistar rats. Administration of tetragastrin in depot form during instillation of MNNG resulted in significant decreases in the incidences of mucosal erosions, ulcerations, and atypical regenerative glandular hyperplasias in the colonic mucosa, most of these lesions being greater in the distal half of the colon. Administration of tetragastrin also significantly decreased the incidences and/or numbers of colonic tumors in Wk 20 and 35. The distribution of colonic tumors induced in Wk 20 and 35 corresponded well to those of erosions, ulcerations, and atypical regenerative glandular hyperplasias induced during the administration of MNNG. These findings suggest that the effect of tetragastrin in decreasing the incidences of erosions, ulcerations, and atypical regenerative glandular hyperplasias in the colonic mucosa during instillation of MNNG is related to its effect in reducing the development of colonic tumors.

Topics: Animals; Colonic Neoplasms; Drug Administration Schedule; Gastrins; Intestinal Diseases; Intestinal Mucosa; Methylnitronitrosoguanidine; Rats; Tetragastrin; Time Factors

Motilin, pancreatic polypeptide and gastrin blood concentrations in response to drinking water have been studied in 40 patients with functional bowel disease and compared with results in two groups of healthy control subjects. Patients with slow transit constipation and idiopathic megacolon showed impaired motilin release. Pancreatic polypeptide release was reduced in patients with slow transit constipation, but increased in those with functional diarrhoea. Gastrin release was impaired in all groups complaining of chronic constipation. Circulating motilin, pancreatic polypeptide and gastrin concentrations appear to bear some relationship to intestinal transit time in patients with functional bowel disorders.

Topics: Adult; Colonic Diseases, Functional; Constipation; Diarrhea; Drinking; Female; Gastrins; Humans; Intestinal Diseases; Male; Megacolon; Middle Aged; Motilin; Pancreatic Polypeptide; Water

Eleven adult Basenji dogs with immunoproliferative small intestinal disease (IPSID) were studied. Two items of history related to the digestive tract were characteristic: (i) chronic intractable diarrhea in most dogs, and (ii) progressive emaciation. Anorexia was intermittent in only a few dogs. In addition, skin lesions of various degrees of severity were observed, including alopecia of pinnae and ventrum, hyperpigmentation and hyperkeratosis of pinnae, and necrosis and ulcerations of margins of pinnae. The cause of the skin lesions was not determined; however, hypothyroidism did not appear to contribute to the skin changes. Standard hematologic and serum chemical values were not consistently abnormal. However, a poorly regenerative anemia, mild neutrophilia, and increased aspartate aminotransferase and alanine aminotransferase activities were generally observed in severely affected dogs. The Pelger-Huet anomaly was identified in dog 3. Maldigestion and malabsorption as determined by the N-benzoyl-L-tyrosyl-p-aminobenzoic acid and d-xylose test was documented to varying degrees in dogs with IPSID. Maldigestion was correlated with functional pancreatic exocrine insufficiency. Severe malabsorption was documented in only 3 dogs. Serum gastrin values were evaluated in these dogs because of a prior observation of parietal cell hyperplasia and gastric ulceration. Hypergastrinemia was documented in 3 dogs. Additional studies will be necessary to determine whether an acid hypersecretory state contributes to the pathogenesis of IPSID in Basenjis.

Topics: 4-Aminobenzoic Acid; Animals; Diarrhea; Dog Diseases; Dogs; Female; Gastrins; Hypergammaglobulinemia; Immunoglobulin G; Immunoglobulin M; Intestinal Absorption; Intestinal Diseases; Malabsorption Syndromes; Male; para-Aminobenzoates; Xylose

Increased basal and/or pentagastrin-stimulated gastric acid secretion was observed in 31 of 40 cystic fibrosis (CF) patients as compared to 13 age-matched control volunteers. Fasting serum gastrin level for 20 CF patients of 67.7 +/- 11.1 pg/ml (ranging from 10 to 145 pg/ml) was normal. Meal-stimulated serum gastrin concentrations were not significantly higher for seven CF patients as compared to nine normal subjects. In a rat bioassay, serum extracts from six CF patients produced gastric acid secretion comparable to 250 ng/ml of pentagastrin; significantly (p less than 0.01) greater than the responses produced by serum extracts from six normal subjects. There was no significant correlation of severity of pulmonary disease or steatorrhea with acid secretory results. Fourteen of 16 CF patients biopsied had evidence of proximal small intestinal injury which correlated with basal acid output elevation. Gastric acid hypersecretion in CF patients is due to nongastrin secretagogues and is a cause of proximal small intestinal injury.

Topics: Adolescent; Adult; Animals; Celiac Disease; Child; Child, Preschool; Cystic Fibrosis; Duodenum; Female; Gastric Acid; Gastrins; Humans; Infant; Intestinal Diseases; Lung Diseases, Obstructive; Male; Pentagastrin; Rats; Rats, Inbred Strains; Time Factors

Topics: Bile Acids and Salts; Dietary Fats; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Intestinal Absorption; Intestinal Diseases; Intestine, Small; Jejunum; Male; Middle Aged; Pancreatic Hormones; Secretin; Syndrome; Time Factors

The availability of pure intestinal hormones and the development of radioimmunoassays for their measurement has expedited research into many aspects of gastrointestinal endocrinology. A complex balance evidently exists between the different intestinal hormones and also the rest of the endocrine system. Polyendocrinopathies have been described, and, so far, two diseases due to intestinal hormone excess (Zollinger-Ellison syndrome and the syndrome of watery diarrhea, hypokalemia and achlorhydria) elucidated. It seems likely that many more gastrointestinal endocrine diseases await discovery.

Topics: Cholecystokinin; Diagnosis, Differential; Diarrhea; Digestive System; Endocrine Glands; Esophagogastric Junction; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Intestinal Diseases; Intestine, Large; Pancreas; Peptic Ulcer; Prostaglandins; Pylorus; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Animals; Gastrins; Hyperplasia; Intestinal Diseases; Intestine, Small; Liver; Liver Diseases; Male; Organ Size; Rats

Topics: Body Temperature; Colon; Computers; Fluoroscopy; Gastrins; Gastrointestinal Motility; Humans; Ileum; Intestinal Diseases; Intubation, Gastrointestinal; Jejunum; Manometry; Muscle, Smooth; Pressure; Radiometry; Serotonin; Telemetry