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PPI AND Gastrin

Lei Deng, Pengju Xiong, Yunhui Luo, Xiao Bu, Suokai Qian, Wuzhao Zhong
The present study aimed to elucidate key molecular mechanisms in the progression of diffuse intrinsic pontine glioma (DIPG). The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in the pediatric DIPG samples were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways of DEGs were enriched and analyzed. The protein-protein interaction (PPI) network of the DEGs was constructed and functional modules of the PPI network were disclosed using ClusterONE...
October 2016: Oncology Letters
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
Bin Liang, Chunning Li, Jianying Zhao
Colorectal cancer (CRC) is the most common malignant tumor of digestive system. The aim of this study was to identify gene signatures during CRC and uncover their potential mechanisms. The gene expression profiles of GSE21815 were downloaded from GEO database. The GSE21815 dataset contained 141 samples, including 132 CRC and 9 normal colon epitheliums. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software...
October 2016: Medical Oncology
Thomas G K Breuer, Laura Borker, Daniel R Quast, Andrea Tannapfel, Wolfgang E Schmidt, Waldemar Uhl, Juris J Meier
INTRODUCTION: Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. PATIENTS AND METHODS: Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined...
November 2016: European Journal of Endocrinology
Yoomi Lee, Aleksandra M Urbanska, Yoku Hayakawa, Hongshan Wang, Andrew S Au, Aesis M Luna, Wenju Chang, Guangchun Jin, Govind Bhagat, Julian A Abrams, Richard A Friedman, Andrea Varro, Kenneth K Wang, Malcolm Boyce, Anil K Rustgi, Antonia R Sepulveda, Michael Quante, Timothy C Wang
OBJECTIVE: The incidence of esophageal adenocarcinoma (EAC) is increasing, but factors contributing to malignant progression of its precursor lesion, Barrett's esophagus (BE), have not been defined. Hypergastrinemia caused by long-term use of proton pump inhibitors (PPIs), has been suggested as one possible risk factor. The gastrin receptor, CCK2R, is expressed in the cardia and upregulated in BE, suggesting the involvement of the gastrin-CCK2R pathway in progression. In the L2-IL-1β mouse model, Barrett's-like esophagus arises from the gastric cardia...
July 18, 2016: Oncotarget
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
Kohzo Takebayashi, Toshihiko Inukai
Gastrin is a linear peptide hormone which is secreted mostly in the stomach pyloric antrum G cells. Although the main role of this hormone is the promotion of the secretion of gastric acid from the stomach parietal cells, gastrin can also behave as a growth factor and stimulate gastric cell proliferation. It is also reported that gastrin promotes β cell neogenesis in the pancreatic ductal complex, modest pancreatic β cell replication, and improvement of glucose tolerance in animal models, in which the remodeling of pancreatic tissues is promoted...
August 25, 2015: World Journal of Diabetes
Heung Up Kim
Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use...
July 2015: Clinical Endoscopy
L Lundell, M Vieth, F Gibson, P Nagy, P J Kahrilas
BACKGROUND: Proton pump inhibitors (PPIs) have a well-established safety profile. However, concerns have been raised about a potential relationship between PPI-induced hypergastrinaemia and the development of enterochromaffin-like (ECL) cell hyperplasia, neuroendocrine tumours and gastric cancer during long-term therapy. AIM: To review the effects of long-term PPI use on serum gastrin levels and gastric histopathology. METHODS: A systematic literature search was conducted in PubMed on 21 April 2015 to identify studies reporting the effects of long-term (defined as >3 years) PPI use on gastrin levels and gastric histopathology...
September 2015: Alimentary Pharmacology & Therapeutics
J Dinesh Kumar, Islay Steele, Andrew R Moore, Senthil V Murugesan, Zoltan Rakonczay, Viktoria Venglovecz, D Mark Pritchard, Rodney Dimaline, Laszlo Tiszlavicz, Andrea Varro, Graham J Dockray
The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI)...
July 15, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
Y-M Han, J-M Park, N Kangwan, M Jeong, S Lee, J Y Cho, W J Ko, K B Hahm
Gastrin is the main hormone stimulating gastric acid secretion, but it exerts proliferative and anti-apoptotic actions on various cancer cell types, in addition to its well-known trophic effect on enterochromaffin-like cells. As treatment with proton pump inhibitors (PPIs) increases the biosynthesis and secretion of gastrin, it has been postulated that treatment with PPIs could increase the risk of cancer, especially in Barrett's esophagus, gastric carcinoids, and colorectal cancer (CRC). Some tumors produce gastrin of their own, which can act in an autocrine manner to promote tumor growth...
April 2015: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
S E Attwood, C Ell, J P Galmiche, R Fiocca, J G Hatlebakk, B Hasselgren, G Långström, M Jahreskog, S Eklund, T Lind, L Lundell
BACKGROUND: Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety...
June 2015: Alimentary Pharmacology & Therapeutics
Lars Lundell
UNLABELLED: Gastric acid secretion and its related diseases and their treatments have generated important contributions to gastroenterology and its development as an autonomous medical specialty. The discovery of histamine receptors and the subsequent H2-receptor antagonists (1972) changed the practice of gastroenterology forever. Gastric acid was effectively inhibited and ulcers could be healed to an extent which had not previously been seen. An additional milestone along the same avenue was offered by the identification of hydrogen potassium adenosine triphosphatase (H(+)K(+)-ATPase) as the proton pump of the parietal cell...
June 2015: Scandinavian Journal of Gastroenterology
Yuji Aiba, Yasuhiro Nakano, Yasuhiro Koga, Kenji Takahashi, Yasuhiko Komatsu
A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No...
June 2015: MicrobiologyOpen
Malcolm Boyce, Sally Dowen, Gillian Turnbull, Frans van den Berg, Chun-Mei Zhao, Duan Chen, James Black
AIMS: To compare gastric acid suppression by netazepide, a gastrin/CCK2 receptor antagonist, with that by a proton pump inhibitor (PPI), and to determine if netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia. METHODS: Thirty healthy subjects completed a double-blind, randomized, parallel group trial of oral netazepide and rabeprazole, alone and combined, once daily for 6 weeks. Primary end points were: basal and pentagastrin-stimulated gastric acid and 24 h circulating gastrin and chromogranin A (CgA) at baseline, start and end of treatment, gastric biopsies at baseline and end of treatment and basal and pentagastrin-stimulated gastric acid and dyspepsia questionnaire after treatment withdrawal...
May 2015: British Journal of Clinical Pharmacology
Na Han, Minkyung Oh, Su Min Park, You Jeong Kim, Eun Ju Lee, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Mi-Kyung Kim, Soon Hee Lee, Byoung Doo Rhee, Jeong Hyun Park
OBJECTIVE: Gastrin increases the growth and neogenesis of the islets of Langerhans. Oral proton pump inhibitors (PPIs) increase the circulating gastrin level in animals and humans, but the therapeutic benefit of PPIs for diabetes mellitus has not been resolved. We examined whether treatment with a PPI for ≥2 months affected the glycated hemoglobin (A1C) level in patients with type 2 diabetes. METHODS: The electronic medical records of patients treated at the Busan Paik Hospital in South Korea were examined...
February 2015: Canadian Journal of Diabetes
Jasmohan S Bajaj, I Jane Cox, Naga S Betrapally, Douglas M Heuman, Mitchell L Schubert, Maiyuran Ratneswaran, Phillip B Hylemon, Melanie B White, Kalyani Daita, Nicole A Noble, Masoumeh Sikaroodi, Roger Williams, Mary M E Crossey, Simon D Taylor-Robinson, Patrick M Gillevet
Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions...
November 15, 2014: American Journal of Physiology. Gastrointestinal and Liver Physiology
Kohzo Takebayashi, Shintaro Sakurai, Tatsuhiko Suzuki, Kenichiro Hori, Tomoko Terasawa, Rika Naruse, Kenji Hara, Mariko Suetsugu, Takafumi Tsuchiya, Hiromi Aoki, Takashi Hamasaki, Hiroshi Shuutou, Toshihiko Inukai
The main purpose of the current study was to investigate the effect of a combination of alogliptin [a dipeptydil peptidase (DPP)-4 inhibitor] and lansoprazole [a proton pump inhibitor (PPI)] compared with alogliptin mono-therapy on glycemic control in patients with type 2 diabetes. This study was a multicenter randomized open-label study. One hundred type 2 diabetic patients were randomly assigned to either the alogliptin with lansoprazole group or the alogliptin mono-therapy group. After 3 months of treatment, the changes in hemoglobin (Hb)A1c, fasting plasma glucose (FPG), serum gastrin, homeostasis model assessment (HOMA)-β, and HOMA-insulin resistance (IR) were evaluated...
2014: Endocrine Journal
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