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Gastrin AND Gastric acid

Malcolm Boyce, Katie A Lloyd, D Mark Pritchard
Gastrin controls gastric acid secretion and mucosal cell growth, especially of enterochromaffin-like cells, via gastrin/cholecystokinin-2 receptor (CCK2R) binding and downstream signalling. Studies in animal models, healthy subjects and patients with gastric neuroendocrine tumours provide compelling evidence to justify developing a CCK2R antagonist (CCK2RA) for preventing or treating the trophic effects of hypergastrinaemia or conditions expressing CCK2R, and with or without a proton pump inhibitor, for treating gastric acid-related conditions...
October 3, 2016: Current Opinion in Pharmacology
Mitchell L Schubert
PURPOSE OF REVIEW: The present review summarizes the past year's literature, both clinical and basic science, regarding neuroendocrine and intracellular regulation of gastric acid secretion and proper use of antisecretory medications. RECENT FINDINGS: Gastric acid kills microorganisms, modulates the gut microbiome, assists in digestion of protein, and facilitates absorption of iron, calcium, and vitamin B12. The main stimulants of acid secretion are gastrin, released from antral G cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons...
November 2016: Current Opinion in Gastroenterology
Yoku Hayakawa, Wenju Chang, Guangchun Jin, Timothy C Wang
Gastrin was initially identified as the hormone primarily responsible for gastric acid secretion, but was subsequently shown to be a growth factor for the proximal stomach, acting through the gastrin receptor CCK2R. Studies in the past several decades have explored the role of gastrin, along with its incompletely processed precursors, in cancer development. The growth in long-term PPI use has frequently led to elevations in serum gastrin levels in patients with upper GI disease, including GERD, peptic ulcers, and chronic gastritis...
August 31, 2016: Current Opinion in Pharmacology
Helene Johannessen, David Revesz, Yosuke Kodama, Nikki Cassie, Karolina Skibicka, Perry Barrett, Suzanne Dickson, Jens Holst, Jens Rehfeld, Geoffrey van der Plasse, Roger Adan, Bård Kulseng, Elinor Ben-Menachem, Chun-Mei Zhao, Duan Chen
BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device with leads placed around gastric vagal trunks through an abdominal incision and controlled by wireless device. Body weight, food intake, hunger/satiety, and metabolic parameters were monitored by a comprehensive laboratory animal monitoring system...
August 30, 2016: Obesity Surgery
Ban-Hock Toh
Pernicious anemia is the hematologic manifestation of chronic atrophic gastritis affecting the corpus of the stomach that denudes the gastric mucosa of gastric parietal cells. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10-20 years. The gastritis arises from activation of pathologic Th1 CD4 T cells to gastric H/K ATPase that is normally resident on gastric mucosal secretory membranes. The onset of autoimmune gastritis is marked by circulating parietal cell antibody to gastric H/K ATPase...
August 18, 2016: Immunologic Research
Katsunori Iijima, Tomoyuki Koike, Yasuhiko Abe, Shuichi Ohara, Tooru Shimosegawa
Gastric acid secretion levels are an important determinant of the manifestation of acid-related upper GI diseases such as gastroesophageal reflux disease. We recently reported that gastric acid secretion levels did not change from the 1990s to 2010s in H. pylori-negative asymptomatic Japanese outpatients with a mean age of 63 years old. However, because young people have a quite different lifestyle, including dietary pattern, from elderly people in Japan, it is worth investigating any chronologic changes in gastric acid secretion in younger generations...
2016: Tohoku Journal of Experimental Medicine
Kristin M Aasarød, Masoud Ramezanzadehkoldeh, Maziar Shabestari, Mats P Mosti, Astrid K Stunes, Janne E Reseland, Vidar Beisvag, Erik Fink Eriksen, Arne K Sandvik, Reinhold G Erben, Christiane Schüler, Malcolm Boyce, Bjørn H Skallerud, Unni Syversen, Reidar Fossmark
Epidemiological studies suggest an increased fracture risk in patients taking proton pump inhibitors (PPIs) for long term. The underlying mechanism, however, has been disputed. By binding to the gastric proton pump, PPIs inhibit gastric acid secretion. We have previously shown that proton pump (H(+)/K(+)ATPase beta subunit) KO mice exhibit reduced bone mineral density (BMD) and inferior bone strength compared with WT mice. Patients using PPIs as well as these KO mice exhibit gastric hypoacidity, and subsequently increased serum concentrations of the hormone gastrin...
August 2016: Journal of Endocrinology
R Czekaj, J Majka, A Ptak-Belowska, A Szlachcic, A Targosz, K Magierowska, M Strzalka, M Magierowski, T Brzozowski
The antioxidizing properties of curcumin, a highly pleiotropic substance used for centuries in traditional medicine has been confirmed by numerous experimental and clinical studies. Curcumin exhibits anti-inflammatory, antiproliferative and anti-angiogenic actions inhibiting the development and progression of tumors but the efficacy of this compound to influence gastric acid secretion n in the stomach and to affect the gastric mucosal damage induced by non-topical ulcerogenes such as stress has been little studied...
April 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Jing Chen, Lihong Chen, Philippe Sanseau, Johannes M Freudenberg, Deepak K Rajpal
The gastrointestinal (GI) tract can have significant impact on the regulation of the whole-body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analysis in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, significant changes in the gene expression were observed in both obese mouse groups in the stomach (ob/ob: 959; HFD: 542)...
May 2016: Physiological Reports
Hólmfridur Helgadóttir, David C Metz, Sigrún H Lund, Sveinbjorn Gizurarson, Elin I Jacobsen, Gudrún A Asgeirsdóttir, Yrsa Yngadóttir, Einar S Björnsson
GOALS: To determine the proportion of patients with gastroesophageal reflux disease who are on proton pump inhibitors (PPIs) who could reduce their prior dosage by half, and identify predictors of successful step-down. BACKGROUND: Appropriate hypergastrinemia results from gastric acid inhibition. A gender difference in fasting gastrin with higher levels among women than among men on long-term PPI therapy has been demonstrated. STUDY: Patients with endoscopically verified erosive esophagitis on long-term PPI therapy were randomized double blindly to step down their dose by half or continue with the same dose for 8 weeks...
May 6, 2016: Journal of Clinical Gastroenterology
E Gould, C Clements, A Reed, L Giori, J M Steiner, J A Lidbury, J S Suchodolski, M Brand, T Moyers, L Emery, M K Tolbert
BACKGROUND: Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. OBJECTIVES: Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. ANIMALS: Six healthy adult DSH cats...
May 2016: Journal of Veterinary Internal Medicine
Reidar Fossmark, Shalini Rao, Patricia Mjønes, Bjørn Munkvold, Arnar Flatberg, Andrea Varro, Liv Thommesen, Kristin G Nørsett
The gastric hormone gastrin plays a role in organizing the gastric mucosa. Gastrin also regulates the expression of genes that have important actions in extracellular matrix modelling, including plasminogen activator inhibitor (PAI)-1 which is part of the urokinase plasminogen activator (uPA) system. The uPA system (including PAI-1) is associated with cancer progression, fibrosis and thrombosis. Its biological role in the stomach and molecular mechanisms of action are not well understood. The aim of this study was to examine the effect of PAI-1 on the trophic changes observed in gastric corpus mucosa in hypergastrinemia using PAI-1 and/or HK-ATPase beta subunit knockout (KO) mice...
May 2016: Peptides
Ana Marija Vrkljan, David Grasić, Ivan Kruljac, Marko Nikolić, Jaksa Filipović-Cugura, Monika Ulamec, Ksenija Kovacić, Nenad Babić, Neven Ljubicić
Autoimmune polyglandular syndrome by definition consists of two or more endocrinological insufficiencies or two organ specific autoimmune diseases. There are no stringent criteria for endocrinological evaluation of patients with one endocrine insufficiency. However, detailed endocrinological evaluation should be undertaken in patients with two autoimmune diseases. Additionally, follow up thereafter should be a must in these patients in order to avoid the possibility of not diagnosing subsequent autoimmune diseases that can occur...
December 2015: Acta Clinica Croatica
Zhihao Liu, Yongli Luo, Yunjiu Cheng, Dezhi Zou, Aihong Zeng, Chunhua Yang, Jia Xu, Hong Zhan
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...
April 2016: Experimental Biology and Medicine
Melanie Haffner-Luntzer, Aline Heilmann, Verena Heidler, Astrid Liedert, Thorsten Schinke, Michael Amling, Timur Alexander Yorgan, Annika Vom Scheidt, Anita Ignatius
Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk, because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet...
March 4, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Jill P Smith, Lionel K Fonkoua, Terry W Moody
The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism...
2016: International Journal of Biological Sciences
M Hansen, M J Scheltema, D P Sonne, J S Hansen, M Sperling, J F Rehfeld, J J Holst, T Vilsbøll, F K Knop
AIM: To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide, glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake. METHODS: On four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo...
June 2016: Diabetes, Obesity & Metabolism
Sinju Sundaresan, Anthony J Kang, Michael M Hayes, Eun-Young K Choi, Juanita L Merchant
BACKGROUND: Gastric carcinoids are slow growing neuroendocrine tumours arising from enterochromaffin-like (ECL) cells in the corpus of stomach. Although most of these tumours arise in the setting of gastric atrophy and hypergastrinemia, it is not understood what genetic background predisposes development of these ECL derived tumours. Moreover, diffuse microcarcinoids in the mucosa can lead to a field effect and limit successful endoscopic removal. OBJECTIVE: To define the genetic background that creates a permissive environment for gastric carcinoids using transgenic mouse lines...
February 9, 2016: Gut
Ian M Rogers
The cause of pyloric stenosis of infancy (PS) is at present unknown. A theory of causation is proposed which is consistent with all the known clinical features of this condition. It is based on the knowledge that PS babies are hypersecretors of acid which pre-dates the development of PS and is an inherited constitutional feature. This acidity will become temporarily and dangerously high due to an insensitivity of the negative feed-back between gastrin and gastric acidy within the first few weeks of life. Normal babies who have inherited normal acidity will also experience peak acid secretions at that time but will be much less acid than babies destined to develop PS...
November 26, 2015: Medical Hypotheses
Andrew C McCourt, Kirsty L O'Donovan, Eva Ekblad, Elin Sand, David Craufurd, Anne Rosser, David Sanders, Nicholas Stoy, Hugh Rickards, Nils Wierup, Gillian P Bates, Maria Björkqvist, Oliver Quarrell
Weight loss is an important complication of Huntington's disease (HD), however the mechanism for weight loss in HD is not entirely understood. Mutant huntingtin is expressed in the gastrointestinal (GI) tract and, in HD mice, mutant huntingtin inclusions are found within the enteric nervous system along the GI tract. A reduction of neuropeptides, decreased mucosal thickness and villus length, as well as gut motility impairment, have also been shown in HD mice. We therefore set out to study gastric mucosa of patients with HD, looking for abnormalities of mucosal cells using immunohistochemistry...
2015: PLoS Currents
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