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American Journal of Physiology. Gastrointestinal and Liver Physiology

Zhen-Tang Jing, Wei Liu, Chao-Rong Xue, Shu-Xiang Wu, Wan-Nan Chen, Xin-Jian Lin, Xu Lin
Tumor necrosis factor α (TNFα) is a highly pleiotropic cytokine executing biological functions as diverse as cell proliferation, metabolic activation, inflammatory responses and cell death. TNFα can induce multiple mechanisms to initiate apoptosis in hepatocytes leading to the subsequent liver injury. Since the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is known to have a protective role in death factor-mediated apoptosis, it is our hypothesis that activation of Akt may represent a therapeutic strategy to alleviate TNFα-induced hepatocyte apoptosis and liver injury...
January 10, 2019: American Journal of Physiology. Gastrointestinal and Liver Physiology
Dafne Balemans, Javier Aguilera-Lizarraga, Morgane V Florens, Piyush Jain, Alexandre Denadai-Souza, Maria Francesca Viola, Yeranddy Aguiar Alpizar, Schalk Van Der Merwe, Pieter Vanden Berghe, Karel Talavera, Stephen J Vanner, Mira M Wouters, Guy E Boeckxstaens
Previously, we showed histamine-mediated sensitization of TRP vanilloid 1 (TRPV1) in patients with irritable bowel syndrome (IBS). Sensitization of TRP ankyrin 1 (TRPA1) and TRP vanilloid 4 (TRPV4) are also involved in aberrant pain perception in preclinical models of somatic pain. Here, we hypothesize that in parallel with TRPV1, histamine sensitizes TRPA1 and TRPV4, contributing to increased visceral pain in patients with IBS. Rectal biopsies were collected from IBS patients and healthy subjects (HS) to study neuronal sensitivity to TRPA1 and TRPV4 agonists (cinnamaldehyde and GSK1016790A) using intracellular Ca2+ imaging...
January 10, 2019: American Journal of Physiology. Gastrointestinal and Liver Physiology
Cole B Enns, John C S Harding, Matthew E Loewen
Brachyspiraspp. causediarrheal disease in multiple animal species by colonization of the colon, resulting in colitis, mucus induction and disrupted ion transport. Unique to spirochete pathogenesisis the immense production of mucus resulting in a niche mucin environment likely favoring spirochete colonization. Mucin rheological properties are heavily influencedby anionic secretion and loss of secretory function has been implicated in diseases such as cystic fibrosis. Here, the effects on the agonist-inducedelectrogenicanionic secretory response by infectious colonic spirochete bacteria Brachyspirahyodysenteriaeand Brachyspira hampsoniiwere assessedin the proximal, apex and distal sections of colonin Ussing chambers...
January 10, 2019: American Journal of Physiology. Gastrointestinal and Liver Physiology
Jessica P Otis, Meng-Chieh Shen, Blake A Caldwell, Oscar E Reyes Gaido, Steven A Farber
Difficulty in imaging the vertebrate intestine in vivo has hindered our ability to model nutrient and protein trafficking from both the luminal and basolateral aspects of enterocytes. Our goal was to use live confocal imaging to increase understanding of intestinal trafficking of dietary cholesterol and apolipoprotein A-I (APOA-I), the main structural component of high-density lipoproteins (HDL). We developed a novel assay to visualize live dietary cholesterol trafficking in the zebrafish intestine by feeding TopFluor-cholesterol (TF-cholesterol), a fluorescent cholesterol analog, in a lipid-rich, chicken egg yolk feed...
January 10, 2019: American Journal of Physiology. Gastrointestinal and Liver Physiology
Patricia D Finn, David Rodriguez, Jill Kohler, Zhengfeng Jiang, Sindy Wan, Erick Blanco, Andrew J King, Tao Chen, Noah Bell, Dean Dragoli, Jeffrey W Jacobs, Rakesh Jain, Michael Leadbetter, Matthew Siegel, Christopher W Carreras, Samantha Koo-McCoy, Karen Shaw, Cathy Le, Sandra Vanegas, I-Hsin Hsu, Kenji Kozuka, Keiko Okamoto, Jeremy S Caldwell, Jason G Lewis
TGR5 agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L-cells, a potentially therapeutic action against metabolic diseases like non-alcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects including inhibition of gallbladder emptying. Here, we characterize RDX8940, a novel, orally administered TGR5 agonist designed to have minimal systemic effects, and investigate its activity in mice fed a Western diet, a model of NAFLD and mild insulin resistance...
January 3, 2019: American Journal of Physiology. Gastrointestinal and Liver Physiology
Åke Nilsson, Rui-Dong Duan
The digestion of choline phospholipids is important for choline homeostasis, lipid signalling, postprandial lipid and energy metabolism, and interaction with intestinal bacteria. The digestion is mediated by the combined action of pancreatic and mucosal enzymes. In the proximal small intestine hydrolysis of phosphatidylcholine (PC) to 1-lyso-PC and FFA by the pancreatic phospholipase A2 IB coincides with the digestion of the dietary triacylglycerols by lipases, but part of the PC digestion is extended and must be mediated by other enzymes as the jejunoileal brush border phospholipase B/lipase and mucosal secreted phospholipase A2 X...
December 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Natacha Germain, Joyceline Cuenco, Yiin Ling, James S Minnion, Serban Bageacu, Dominique Grouselle, Bruno Estour, Bogdan Galusca
INTRODUCTION: Activation of ghrelin is controlled by the enzyme Ghrelin-O-Acyl Transferase (GOAT). In humans, localization of this acylation is poorly understood. The aim of that study was to explore GOAT localization and activation in human Liver by evaluating both bioactive and non-bioactive ghrelin in the blood stream entering and leaving liver and to simultaneously evaluate GOAT mRNA expression in Liver. METHODS: Healthy part of oncologic hepatic tissue collected from nine patients undergoing hepatectomy was used to evaluate GOAT mRNA expression by quantitative real time polymerase chain reaction (RTqPCR)...
December 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Timothy C Wang, Martin G Martin, Calvin J Kuo, Ophir D Klein, Joyce C Niland
No abstract text is available yet for this article.
December 14, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Aurelio Mauro, Farhan Quader, Salvatore Tolone, Edoardo Savarino, Nicola De Bortoli, Marianna Franchina, C Prakash Gyawali, Roberto Penagini
BACKGROUND: Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink challenge (RDC) are complementary tests used during high resolution manometry (HRM) that evaluate inhibitory and excitatory neuromuscular function and latent obstruction respectively. Methods&aim. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 males; 63; 54-70 years). Twenty one healthy subjects (11 males; 28; 26-30 years) were used as a control group...
December 13, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Takanori Konishi, Rebecca M Schuster, Alex B Lentsch
Liver recovery after hepatic ischemia/reperfusion (I/R) injury is characterized by clearance of dead tissue and its replacement with functional liver parenchyma. Previous reports have observed fibrosis after liver I/R. In order to determine if liver fibrosis after I/R was a pathologic consequence of the injury response, we assessed the development of liver fibrosis after I/R and its impact on subsequent insult. A murine model of partial I/R was used to induce liver injury and study the reparative response. During liver remodeling after I/R, expression of the pro-fibrotic genes increased in the ischemic liver...
December 13, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Rana Al-Sadi, Moustafa Youssef, Manmeet Rawat, Shuhong Guo, Karol Dokladny, Mohammad Haque, D Martin Watterson, Thomas Y Ma
Matrix Metalloproteinase-9 (MMP-9) has been implicated to be an important pathogenic factor in inflammatory bowel disease (IBD). MMP-9 is markedly elevated in intestinal tissue of patients with IBD, and IBD patients have a defective intestinal tight junction (TJ) barrier manifested by an increase in intestinal permeability. The loss of intestinal barrier function is a contributing factor in the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The purpose of this study was to investigate the effect of MMP-9 on intestinal epithelial TJ barrier and to delineate the intracellular mechanisms involved using in-vitro and in-vivo model systems...
December 13, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Rachel K Zwick, Benjamin Ohlstein, Ophir D Klein
The gastrointestinal (GI) tract renews frequently to sustain nutrient digestion and absorption in the face of consistent tissue stress. In many species, proliferative intestinal stem cells (ISCs) are responsible for repairing the damage arising from chemical and mechanical aspects of food breakdown and exposure to pathogens. As the cellular source of all mature cell types of the intestinal epithelium throughout adulthood, ISCs hold tremendous therapeutic potential for understanding and treating GI disease in humans...
December 13, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Kathryn A Hasenstab, Saira Nawaz, Ivan M Lang, Reza Shaker, Sudarshan R Jadcherla
OBJECTIVE: Aims were to: 1) examine pharyngo-esophageal and cardio-respiratory responses to provoking pharyngeal stimuli, and 2) determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardio-respiratory events occurring in preterm infants. METHODS: Forty-eight neonates (29 males, born at 27.7 ± 0.5 wks; Mean ± SEM) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wks postmenstrual age using concurrent pharyngo-esophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor...
December 13, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Beatrix Pfanzagl, Victor F Zevallos, Detlef Schuppan, Roswitha Pfragner, Erika Jensen-Jarolim
The P-STS human ileal neuroendocrine tumor cells, as a model for gut enterochromaffin cells, are strongly and synergistically activated by histamine plus acetylcholine (ACh), presumably via histamine 4 receptors, and weakly activated by histamine alone. Sensing these signals, enterochromaffin cells could participate in intestinal intolerance or allergic reactions to food constituents associated with elevated histamine levels. In this study we aimed to analyze the underlying molecular mechanisms. Inhibition by mepyramine and mibefradil indicated that histamine alone caused a rise in [Ca2+ ]i via histamine 1 receptors involving T-type voltage-gated calcium channels (VGCCs)...
December 12, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Irene Ramos-Álvarez, Lingaku Lee, Robert T Jensen
Rat pancreatic acinar cells possess only the p21-activated kinase (PAKs), PAK4 of the Group-II p21-activated kinase (PAK) and it is activated by gastrointestinal hormones/neurotransmitters stimulating PLC and by a number of growth factors. However, little is known generally of cAMP-agents causing PAK4 activation and there are no studies with gastrointestinal hormones/neurotransmitters activating cAMP cascades. In the present study, we examined the ability of VIP and secretin, which stimulate cAMP generation in pancreatic acini, to stimulate PAK4 activation, the signaling cascades involved and its possible role in activating Na+,K+ATPase...
December 6, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Jon N Buzzelli, Louise O'Connor, Michelle Scurr, Sharleen Chung Nien Chin, Angelique Catubig, Garrett Z Ng, Masanobu Oshima, Hiroko Oshima, Andrew S Giraud, Philip Sutton, Louise M Judd, Trevelyan R Menheniott
Expression of the cytokine IL-11 is elevated in human Helicobacter pylori infection and progressively increases with worsening gastric pathology. Additionally, IL-11 is required for tumour development in STAT3 dependent murine models of gastric cancer (GC) and, when administered acutely, causes resolving atrophic gastritis. However, it is unclear whether locally elevated IL-11 ligand expression can, in isolation from oncogenic gp130-JAK-STAT pathway mutations, initiate GC pathogenesis. Here we developed a transgenic mouse model of stomach-specific (keratin 19 promoter) IL-11 ligand overexpression...
December 6, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Louis R Parham, Patrick A Williams, Priya Chatterji, Kelly A Whelan, Kathryn E Hamilton
Intestinal epithelial cells are among the most rapidly proliferating cell types in the human body. There are several different sub-types of epithelial cells, each with unique functional roles in responding to the ever-changing environment. The epithelium's ability for rapid and customized responses to environmental changes requires multi-tiered levels of gene regulation. An emerging paradigm in gastrointestinal epithelial cells is the regulation of functionally-related mRNA families, or regulons, via RNA binding proteins (RBPs)...
December 6, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Carsten Dirksen, Jesper Graff, Stefan Fuglsang, Jens F Rehfeld, Jens J Holst, Jan Lysgård Madsen
Dietary fat, and particularly fatty acids from hydrolyzed triglycerides, reduce appetite, whereas, paradoxically, a high-fat diet leads to excess calorie intake and weight gain. We therefore hypothesized that the appetite-regulating effects of dietary fat is perturbed in obesity. Ten men with severe obesity (median BMI 51.0 kg/m2 [range 47.9 to 69.0]) and 10 non-obese men (BMI 24.6 kg/m2 [21.7 to 26.8]) were recruited for a double-blind randomized crossover study. On two occasions separated by at least one week, participants were given isocaloric (2660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain fatty acid) or olive oil (triglyceride) containing radiolabeled lipid and water markers...
December 6, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Derek J Nunez, Myriam Alexander, Laura Yerges-Armstrong, Gurparkash Singh, Geert Byttebier, Elisa Fabbrini, Dawn Waterworth, Gary Meininger, Nicholas Galwey, Lars Wallentin, Harvey D White, Bart Vannieuwenhuyse, William Alazawi, Stuart Kendrick, Naveed Sattar, Ele Ferrannini
Liver enzyme concentrations are measured as safety endpoints in clinical trials to detect drug-related hepatotoxicity, but little is known about the epidemiology of these biomarkers in subjects without hepatic dysfunction who are enrolled in drug trials. We studied alanine and aspartate aminotransferase (ALT, AST) in subjects randomized to placebo who completed assessments over 36 months in a cardiovascular outcome trial (the 'STABILITY' trial; n=4264; mean age: 64.2 yr) or over 12 months in 3 trials that enrolled only subjects with type 2 diabetes (T2D) (the 'DIA' trials; n=308; mean age: 62...
November 29, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Olga Y Gasheva, Irina Tsoy Nizamutdinova, Laura Hargrove, Cassidy Gobbell, Maria Troyanova-Wood, Sally F Alpini, Sarit Pal, Christina Du, Angie R Hitt, Vlad V Yakovlev, M Karen Newell-Rogers, David Carl Zawieja, Cynthia J Meininger, Gianfranco D Alpini, Heather Francis, Anatoliy A Gashev
This study aimed to establish mechanistic links between the prolonged intake of desloratadine, a common H1 receptor blocker (i.e. antihistamine), and development of obesity and metabolic syndrome. Male Sprague-Dawley rats were treated orally for 16 weeks with desloratadine. We analyzed the dynamics of body weight gain; tissue fat accumulation/density; contractility of isolated mesenteric lymphatic vessels; levels of blood lipids, glucose and insulin; together with parameters of liver function. Prolonged intake of desloratadine induced development of an obesity-like phenotype and signs of metabolic syndrome...
November 26, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
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