4,980 results match your criteria American Journal of Physiology - Gastrointestinal and Liver Physiology [Journal]


Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 15. Epub 2019 Feb 15.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

A large number of glucagon-like-peptide 1 (GLP-1) and peptide-YY (PYY) producing L-cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3. Read More

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http://dx.doi.org/10.1152/ajpgi.00010.2019DOI Listing
February 2019

Mucosal RNA and Protein Expression as the next frontier in IBS: abnormal function despite morphologically intact small intestinal Mucosa.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 15. Epub 2019 Feb 15.

University Hospital Vall d'Hebron, Barcelona.

Irritable bowel syndrome is one of the commonest gastrointestinal disorders. Although long-time considered a pure functional disorder, intense research in past years has rendered a very complex and varied array of observations indicating the presence of structural and molecular abnormalities underlying characteristic motor and sensitive changes and clinical manifestations. Analysis of gene and protein expression in the intestinal mucosa has shed light on the molecular mechanisms implicated in IBS physiopathology. Read More

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http://dx.doi.org/10.1152/ajpgi.00186.2018DOI Listing
February 2019

Gut microbiota in liver disease: Too much is harmful, nothing at all is not helpful either.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 15. Epub 2019 Feb 15.

Medicine, UCSD, United States.

The intestinal microbiome plays an major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated deleterious effects on its host. Reducing the number of intestinal bacteria with antibiotic treatment is generally advantageous in experimental liver diseases. Complete absence of intestinal microbiota as in germ-free rodents can be protective in autoimmune hepatitis, and hepatic tumors induced by chemicals; or it can exacerbate disease as in acute toxic liver injury and liver fibrosis/cirrhosis. Read More

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http://dx.doi.org/10.1152/ajpgi.00370.2018DOI Listing
February 2019
1 Read

The Role of Ketone Signaling in the Hepatic Response to Fasting.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 15. Epub 2019 Feb 15.

School of Animal and Comparative Biomedical Scieces, U. Arizona, United States.

Ketosis is a metabolic adaptation to fasting, non-alcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G-protein coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. Read More

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http://dx.doi.org/10.1152/ajpgi.00415.2017DOI Listing
February 2019
1 Read

Necrostatin-1 accelerates time to death in a rat model of cecal ligation and puncture and massively increases hepatocyte caspase-3 cleavage.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 8. Epub 2019 Feb 8.

Pathophysiology, Guangdong Key Lab of Shock and Microcirculation Research, China.

Necroptosis, a form of regulated necrosis, has been reported to be involved in numerous pathologies, including sepsis. However, a protective effect of the selective inhibitor of necroptosis, necrostatin-1 (Nec-1), against sepsis remains to be confirmed. Animals (rats and mice) were subjected to cecal ligation and puncture (CLP) to mimic clinical sepsis. Read More

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http://dx.doi.org/10.1152/ajpgi.00175.2018DOI Listing
February 2019

Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 8. Epub 2019 Feb 8.

ADEN group EA 4311, Rouen University, France.

Background: Inflammatory bowel diseases (IBD) are characterized by flares repetition and remission periods leading to chronic post-inflammatory sequels. Among them, one third of IBD patients are suffering from persisting functional symptoms or psychological comorbidities during remission. Our study aimed to assess functional and behavioral sequels of chronic colitis in rats with quiescent intestinal inflammation. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00248.2018
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http://dx.doi.org/10.1152/ajpgi.00248.2018DOI Listing
February 2019
2 Reads

lncRNA GAS5 Restrains CCl-Induced Hepatic Fibrosis by Targeting miR-23a through the PTEN/PI3K/Akt Signaling Pathway.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 8. Epub 2019 Feb 8.

College of Traditional Mongolia Medicine, Inner Mongolia Medical University.

Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that lncRNA GAS5, miR-23a and PTEN play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a and PTEN in the pathological process of hepatic fibrosis and HSC activation. Read More

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http://dx.doi.org/10.1152/ajpgi.00249.2018DOI Listing
February 2019

Preservation of Reserve Intestinal Epithelial Stem Cells following Severe Ischemic Injury.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 4. Epub 2019 Feb 4.

Clinical Sciences, North Carolina State University.

Intestinal ischemia is an abdominal emergency with a mortality rate >50%, leading to epithelial barrier loss and subsequent sepsis. Epithelial renewal and repair after injury depend on intestinal epithelial stem cells (ISC) that reside within the crypts of Lieberkühn. Two ISC populations critical to epithelial repair have been described: 1) Active ISC (aISC; highly proliferative; Lgr5+, Sox9+) and 2) reserve ISC (rISC; less proliferative; Hopx+). Read More

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http://dx.doi.org/10.1152/ajpgi.00262.2018DOI Listing
February 2019
2 Reads

Ethanol Withdrawal Mitigates Fatty Liver by Normalizing Lipid Catabolism.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 4. Epub 2019 Feb 4.

Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, United States.

Background: We are investigating the changes in hepatic lipid catabolism that contribute to alcohol-induced fatty liver. Following chronic ethanol exposure, abstinence from alcohol resolves steatosis. Here, we investigated the hepatocellular events that lead to this resolution by quantifying specific catabolic parameters that returned to control levels after EtOH was withdrawn. Read More

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http://dx.doi.org/10.1152/ajpgi.00376.2018DOI Listing
February 2019
1 Read

Chronic Alcohol Exposure Alters Circulating Insulin and Ghrelin Levels: Role of Ghrelin in Hepatic Steatosis.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 31. Epub 2019 Jan 31.

Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, United States.

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of non-esterified free fatty acids (NEFA) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Read More

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http://dx.doi.org/10.1152/ajpgi.00334.2018DOI Listing
January 2019
1 Read

Differential biomechanical properties of mouse distal colon and rectum innervated by the splanchnic and pelvic afferents.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 31. Epub 2019 Jan 31.

Biomedical Engineering, University of Connecticut, United States.

Visceral pain is one of the principal complaints of patients with Irritable Bowel Syndrome (IBS), and this pain is reliably evoked by mechanical distension/stretch of distal colon and rectum (colorectum). This study focuses on the biomechanics of the colorectum that could play critical roles in mechanical neural encoding. We harvested the distal 30 mm of the colorectum from mice, divided evenly into three 10-mm-long segments (colonic, intermediate and rectal), and conducted biaxial mechanical stretch tests and opening-angle measurements for each tissue segment. Read More

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http://dx.doi.org/10.1152/ajpgi.00324.2018DOI Listing
January 2019

G Protein-Coupled Receptor Trafficking and Signaling: New Insights into the Enteric Nervous System.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 31. Epub 2019 Jan 31.

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Australia.

G Protein-Coupled Receptors (GPCRs) are essential for the neurogenic control of gastrointestinal (GI) function and are important and emerging therapeutic targets in the gut. Detailed knowledge of both the distribution and functional expression of GPCRs in the enteric nervous system (ENS) is critical to advance our understanding of how these receptors contribute to GI function during physiological and pathophysiological states. Equally important, but less well-defined, is the complex relationship between receptor expression, ligand binding, signaling and trafficking within enteric neurons. Read More

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http://dx.doi.org/10.1152/ajpgi.00406.2018DOI Listing
January 2019

Topographical Plots of Esophageal Distension and Contraction: Effects of Posture on Esophageal Peristalsis and Bolus Transport.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 24. Epub 2019 Jan 24.

Medicine, University of California, San Diego, United States.

Introduction: Each swallow induces a wave of inhibition followed by contraction in the esophagus. Unlike contraction that can easily be measured in humans using high resolution manometry (HRM), inhibition is difficult to measure. Luminal distension is a surrogate of the esophageal inhibition. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00397.2018
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http://dx.doi.org/10.1152/ajpgi.00397.2018DOI Listing
January 2019
2 Reads

HEPATIC TRANSCRIPTOME SIGNATURES IN PATIENTS WITH VARYING DEGREES OF NON-ALCOHOLIC FATTY LIVER DISEASE COMPARED TO HEALTHY NORMAL-WEIGHT INDIVIDUALS.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 17. Epub 2019 Jan 17.

Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, University of Copenhagen, Denmark.

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over non-alcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared to healthy normal-weight and obese individuals. Read More

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http://dx.doi.org/10.1152/ajpgi.00358.2018DOI Listing
January 2019
2 Reads

Defective FXR-FGF15 signaling and bile acid homeostasis in cystic fibrosis mice can be restored by the laxative polyethylene glycol.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 17. Epub 2019 Jan 17.

Section of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, Netherlands.

The gastrointestinal phenotype of cystic fibrosis (CF) features intestinal bile acid (BA) malabsorption, impaired intestinal farnesoid X receptor (FXR) activation and consequently reduced fibroblast growth factor 19 (FGF19, FGF15 in mice) production. The osmotic laxative polyethylene glycol (PEG) has been shown to decrease intestinal mucus accumulation in CF mice and could, by doing so, improve BA reabsorption. Here we determined the effect of PEG on BA excretion and FXR-FGF15 signaling in CF mice. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00188.2018
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http://dx.doi.org/10.1152/ajpgi.00188.2018DOI Listing
January 2019
9 Reads

AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 10;316(3):G387-G396. Epub 2019 Jan 10.

Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou , China.

Tumor necrosis factor-α (TNF-α) is a highly pleiotropic cytokine executing biological functions as diverse as cell proliferation, metabolic activation, inflammatory responses, and cell death. TNF-α 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 TNF-α-induced hepatocyte apoptosis and liver injury. Read More

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http://dx.doi.org/10.1152/ajpgi.00350.2018DOI Listing
March 2019
2 Reads

Histamine-mediated potentiation of transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 signaling in submucosal neurons in patients with irritable bowel syndrome.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 10;316(3):G338-G349. Epub 2019 Jan 10.

Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven , Leuven , Belgium.

Previously, we showed histamine-mediated sensitization of transient receptor potential (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. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00116.2018
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http://dx.doi.org/10.1152/ajpgi.00116.2018DOI Listing
March 2019
2 Reads

Decreased Electrogenic Anionic Secretory Response in the Porcine Colon Following in vivo Challenge with Brachyspira spp. Supports an Altered Mucin Environment.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 10. Epub 2019 Jan 10.

Veterinary Biomedical Sciences, University of Saskatchewan, Canada.

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. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00348.2018
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http://dx.doi.org/10.1152/ajpgi.00348.2018DOI Listing
January 2019
5 Reads

Dietary cholesterol and apolipoprotein A-I are trafficked in endosomes and lysosomes in the live zebrafish intestine.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 10;316(3):G350-G365. Epub 2019 Jan 10.

Department of Embryology, Carnegie Institution for Science , Baltimore, Maryland.

Difficulty in imaging the vertebrate intestine in vivo has hindered our ability to model nutrient and protein trafficking from both the lumenal 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. 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. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00080.2018
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http://dx.doi.org/10.1152/ajpgi.00080.2018DOI Listing
March 2019
5 Reads

Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 3. Epub 2019 Jan 3.

Ardelyx, Inc., United States.

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. Read More

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http://dx.doi.org/10.1152/ajpgi.00300.2018DOI Listing
January 2019
2 Reads
3.798 Impact Factor

Pancreatic and mucosal enzymes in choline phospholipid digestion.

Am J Physiol Gastrointest Liver Physiol 2018 Dec 21. Epub 2018 Dec 21.

Department of Clinical Sciences, Lund University, Sweden.

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. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00320.2018
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http://dx.doi.org/10.1152/ajpgi.00320.2018DOI Listing
December 2018
14 Reads

Ghrelin acylation by ghrelin- O-acyltransferase can occur in healthy part of oncological liver in humans.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 21;316(3):G366-G371. Epub 2018 Dec 21.

Division of Endocrinology, CHU Saint-Etienne, Saint-Etienne , France.

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 this study is to explore GOAT localization and activation in the human liver by evaluating both bioactive and non-bioactive ghrelin in the bloodstream entering and leaving the liver and to simultaneously evaluate GOAT mRNA expression in the liver. Read More

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http://dx.doi.org/10.1152/ajpgi.00143.2018DOI Listing
March 2019
1 Read

Enterotoxigenic Escherichia coli heat labile enterotoxin inhibits intestinal ascorbic acid uptake via a cAMP-dependent NF-κB-mediated pathway.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 4;316(1):G55-G63. Epub 2018 Oct 4.

Department of Medicine, University of California , Irvine, California.

Vitamin C is an antioxidant and acts as a cofactor for many enzymatic reactions. Humans obtain vitamin C from dietary sources via intestinal absorption, a process that involves the sodium-dependent vitamin C transporters-1 and -2 (SVCT1 and SVCT2). Enterotoxigenic Escherichia coli (ETEC) infection impacts intestinal absorption/secretory functions, but nothing is known about its effect on ascorbic acid (AA) uptake. Read More

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http://dx.doi.org/10.1152/ajpgi.00259.2018DOI Listing
January 2019
1 Read

Molecular characterization of a precision-cut rat liver slice model for the evaluation of antifibrotic compounds.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 8;316(1):G15-G24. Epub 2018 Nov 8.

Bristol-Myers Squibb, Pennington, New Jersey.

Precision-cut liver tissue slice (PCLS) contains all major cell types of the liver parenchyma and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study liver fibrosis and test the antifibrotic effect of experimental compounds in a physiological environment. In this study using RNA sequencing, we demonstrated that various pathways functionally related to fibrotic mechanisms were dysregulated in PCLSs derived from rats subjected to bile duct ligation. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00281.2018
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http://dx.doi.org/10.1152/ajpgi.00281.2018DOI Listing
January 2019
11 Reads

Introduction to themed series on intestinal stem cells and the NIDDK Intestinal Stem Cell Consortium.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 14;316(2):G247-G250. Epub 2018 Dec 14.

Department of Diabetes and Cancer Discovery Science, City of Hope Comprehensive Cancer Center, Duarte, California.

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http://dx.doi.org/10.1152/ajpgi.00146.2018DOI Listing
February 2019
1 Read

Provocative testing in patients with jackhammer esophagus: evidence for altered neural control.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 13;316(3):G397-G403. Epub 2018 Dec 13.

Department of Pathophysiology and Transplantation, Università degli Studi di Milano , Milan , Italy.

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. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 men; median age: 63 yr; IQR: 54-70 yr). Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00342.2018
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http://dx.doi.org/10.1152/ajpgi.00342.2018DOI Listing
March 2019
5 Reads

Liver repair and regeneration after ischemia-reperfusion injury is associated with prolonged fibrosis.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 13;316(3):G323-G331. Epub 2018 Dec 13.

Department of Surgery, College of Medicine, University of Cincinnati , Cincinnati, Ohio.

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. To determine whether 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. Read More

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http://dx.doi.org/10.1152/ajpgi.00154.2018DOI Listing
March 2019
1 Read

MMP-9-induced increase in intestinal epithelial tight permeability is mediated by p38 kinase signaling pathway activation of MLCK gene.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 13;316(2):G278-G290. Epub 2018 Dec 13.

Penn State Milton S. Hershey Medical Center, College of Medicine , Hershey, Pennsylvania.

Matrix metalloproteinase-9 (MMP-9) has been implicated as being 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 epithelial barrier function is an important contributing factor in the development and prolongation of intestinal inflammation; however, the role of MMP-9 in intestinal barrier function remains unclear. Read More

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http://dx.doi.org/10.1152/ajpgi.00126.2018DOI Listing
February 2019
1 Read

Intestinal renewal across the animal kingdom: comparing stem cell activity in mouse and Drosophila.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 13;316(3):G313-G322. Epub 2018 Dec 13.

Program in Craniofacial Biology and Department of Orofacial Sciences, University of California , San Francisco, California.

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 the repair of 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. Read More

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http://dx.doi.org/10.1152/ajpgi.00353.2018DOI Listing
March 2019
1 Read

Pharyngoesophageal and cardiorespiratory interactions: potential implications for premature infants at risk of clinically significant cardiorespiratory events.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 13;316(2):G304-G312. Epub 2018 Dec 13.

Innovative Neonatal and Infant Feeding Disorders Research Program, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio.

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0. Read More

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http://dx.doi.org/10.1152/ajpgi.00303.2018DOI Listing
February 2019
2 Reads
3.798 Impact Factor

Histamine causes influx via T-type voltage-gated calcium channels in an enterochromaffin tumor cell line: potential therapeutic target in adverse food reactions.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 12;316(2):G291-G303. Epub 2018 Dec 12.

Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna , Vienna , Austria.

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. Read More

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http://dx.doi.org/10.1152/ajpgi.00261.2018DOI Listing
February 2019
5 Reads

Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of Na,K-ATPase in pancreatic acinar cells.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 6;316(2):G263-G277. Epub 2018 Dec 6.

Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland.

Rat pancreatic acinar cells possess only the p21-activated kinase (PAKs), PAK4 of the group II 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 their possible role in activating sodium-potassium adenosine triphosphatase (Na,K-ATPase). Read More

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http://dx.doi.org/10.1152/ajpgi.00275.2018DOI Listing
February 2019
5 Reads

Overexpression of IL-11 promotes premalignant gastric epithelial hyperplasia in isolation from germline gp130-JAK-STAT driver mutations.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 6;316(2):G251-G262. Epub 2018 Dec 6.

Murdoch Children's Research Institute, The Royal Children's Hospital , Parkville, Victoria , Australia.

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 tumor 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. Read More

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http://dx.doi.org/10.1152/ajpgi.00304.2018DOI Listing
February 2019
2 Reads

RNA regulons are essential in intestinal homeostasis.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 6;316(1):G197-G204. Epub 2018 Dec 6.

Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania.

Intestinal epithelial cells are among the most rapidly proliferating cell types in the human body. There are several different subtypes 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 multitiered levels of gene regulation. Read More

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http://dx.doi.org/10.1152/ajpgi.00403.2017DOI Listing
January 2019
6 Reads

Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 6;316(3):G332-G337. Epub 2018 Dec 6.

Department of Clinical Physiology and Nuclear Medicine, Centre for Functional Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark.

Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51. Read More

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http://dx.doi.org/10.1152/ajpgi.00310.2018DOI Listing
March 2019
3 Reads

Factors influencing longitudinal changes of circulating liver enzyme concentrations in subjects randomized to placebo in four clinical trials.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 29;316(3):G372-G386. Epub 2018 Nov 29.

Consiglio Nazionale delle Recerche Institute of Clinical Physiology, Pisa , Italy.

Liver enzyme concentrations are measured as safety end points 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 and AST) in subjects randomized to placebo who completed assessments over 36 mo in a cardiovascular outcome trial [the Stabilisation of Atherosclerotic Plaque by Initiation of Darapladib Therapy ("STABILITY") trial; n = 4,264; mean age: 64.2 yr] or over 12 mo in three trials that enrolled only subjects with type 2 diabetes (T2D) [the DIA trials; n = 308; mean age: 62. Read More

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http://dx.doi.org/10.1152/ajpgi.00051.2018DOI Listing
March 2019
2 Reads

Prolonged intake of desloratadine: mesenteric lymphatic vessel dysfunction and development of obesity/metabolic syndrome.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 26;316(1):G217-G227. Epub 2018 Nov 26.

Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, Texas.

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. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00321.2018
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http://dx.doi.org/10.1152/ajpgi.00321.2018DOI Listing
January 2019
15 Reads

Distinct roles of histamine H1- and H2-receptor signaling pathways in inflammation-associated colonic tumorigenesis.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 21;316(1):G205-G216. Epub 2018 Nov 21.

Department of Pathology and Immunology, Baylor College of Medicine , Houston, Texas.

Inflammatory bowel disease (IBD) is a well-known risk factor for the development of colorectal cancer. Prior studies have demonstrated that microbial histamine can ameliorate intestinal inflammation in mice. We tested the hypothesis whether microbe-derived luminal histamine suppresses inflammation-associated colon cancer in Apc mice. Read More

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http://dx.doi.org/10.1152/ajpgi.00212.2018DOI Listing
January 2019
11 Reads

Corrigendum.

Authors:

Am J Physiol Gastrointest Liver Physiol 2018 Nov;315(5):G908

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http://dx.doi.org/10.1152/ajpgi.zh3-7539-corr.2018DOI Listing
November 2018
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A novel role for programmed cell death receptor ligand 2 in sepsis-induced hepatic dysfunction.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 15;316(1):G106-G114. Epub 2018 Nov 15.

Division of Surgical Research/Department of Surgery, Lifespan-Rhode Island Hospital and Brown University , Providence, Rhode Island.

The liver is an organ that, when dysfunctional in a septic patient, is strongly associated with morbidity and mortality. Understanding the pathophysiology of liver failure during sepsis may lead to improved diagnostics and potential therapeutic targets. Historically, programmed cell death receptor (PD) ligand 1 (PD-L1) has been considered the primary ligand for its checkpoint molecule counterpart, PD-1, with PD-L2 rarely in the immunopathological spotlight. Read More

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http://dx.doi.org/10.1152/ajpgi.00204.2018DOI Listing
January 2019
6 Reads

Water intake increases mesenteric lymph flow and the total flux of albumin, long-chain fatty acids, and IL-22 in rats: new concept of absorption in jejunum.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 15;316(1):G155-G165. Epub 2018 Nov 15.

Department of Innovation of Medical and Health Sciences Research, Shinshu University School of Medicine , Matsumoto , Japan.

The traditional Japanese health care custom recommends that a suitable volume of water is consumed. However, physiological and immunological mechanisms in support of this practice are unknown. Therefore, we conducted rat and rabbit in vivo experiments to investigate the effects of intragastric administration of distilled water on the jejunal-originated lymph flow and the concentrations and total flux of cells, albumin, long-chain fatty acids, and innate lymphoid cell 3 (ILC-3)-secreted interleukin-22 (IL-22) through mesenteric lymph vessels. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00325.2018
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http://dx.doi.org/10.1152/ajpgi.00325.2018DOI Listing
January 2019
6 Reads

Transgenic expression of cyclooxygenase-2 in pancreatic acinar cells induces chronic pancreatitis.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 15;316(1):G179-G186. Epub 2018 Nov 15.

Department of Cancer Biology, Mayo Clinic , Jacksonville, Florida.

Replacement of the exocrine parenchyma by fibrous tissue is a main characteristic of chronic pancreatitis. Understanding the mechanisms of pancreatic fibrogenesis is critical for the development of preventive and therapeutic interventions. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin synthesis, is expressed in patients with chronic pancreatitis. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00096.2018
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http://dx.doi.org/10.1152/ajpgi.00096.2018DOI Listing
January 2019
10 Reads

Molecular characterization of a precision-cut rat liver slice model for the evaluation of antifibrotic compounds.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 8;316(1):G15-G24. Epub 2018 Nov 8.

Bristol-Myers Squibb, Pennington, New Jersey.

Precision-cut liver tissue slice (PCLS) contains all major cell types of the liver parenchyma and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study liver fibrosis and test the antifibrotic effect of experimental compounds in a physiological environment. In this study using RNA sequencing, we demonstrated that various pathways functionally related to fibrotic mechanisms were dysregulated in PCLSs derived from rats subjected to bile duct ligation. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00281.2018
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http://dx.doi.org/10.1152/ajpgi.00281.2018DOI Listing
January 2019
12 Reads

Zinc ameliorates intestinal barrier dysfunctions in shigellosis by reinstating claudin-2 and -4 on the membranes.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 8;316(2):G229-G246. Epub 2018 Nov 8.

Molecular Pathophysiology Division, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata , India.

Whether zinc (Zn) regulates barrier functions by modulating tight-junction (TJ) proteins when pathogens such as Shigella alter epithelial permeability is still unresolved. We investigated the potential benefits of Zn in restoring impaired barrier function in vivo in Shigella-infected mouse tissue and in vitro in T84 cell monolayers. Basolateral Shigella infection triggered a time-dependent decrease in transepithelial resistance followed by an increase in paracellular permeability of FITC-labeled dextran and altered ion selectivity. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00092.2018
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http://dx.doi.org/10.1152/ajpgi.00092.2018DOI Listing
February 2019
7 Reads

LGR4 protects hepatocytes from injury in mouse.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 8;316(1):G123-G131. Epub 2018 Nov 8.

Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan.

Leucine-rich repeat G protein-coupled receptors (LGRs) and their endogenous ligands R-spondin1-4 (Rspo) are critical in embryonic development and in maintenance of stem cells. The functions of the Rspo-LGR system in differentiated cells remain uncharacterized. In this study, the expression profiles of LGRs and Rspos were characterized in mature hepatocytes. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00056.2018
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http://dx.doi.org/10.1152/ajpgi.00056.2018DOI Listing
January 2019
12 Reads

Lipid mediators of liver injury in nonalcoholic fatty liver disease.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 1;316(1):G75-G81. Epub 2018 Nov 1.

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine , Indianapolis, Indiana.

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of histopathological phenotypes ranging from simple steatosis to more severe liver disease associated with cell injury, including nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. Only a subset of patients with NAFLD develop NASH from yet incompletely understood mechanisms. Emerging data suggest lipid species other than triglycerides as contributors to the pathogenesis of NASH. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00170.2018
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http://dx.doi.org/10.1152/ajpgi.00170.2018DOI Listing
January 2019
11 Reads

Absence of the sulfate transporter SAT-1 has no impact on oxalate handling by mouse intestine and does not cause hyperoxaluria or hyperoxalemia.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 1;316(1):G82-G94. Epub 2018 Nov 1.

Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, Florida.

The anion exchanger SAT-1 [sulfate anion transporter 1 (Slc26a1)] is considered an important regulator of oxalate and sulfate homeostasis, but the mechanistic basis of these critical roles remain undetermined. Previously, characterization of the SAT-1-knockout (KO) mouse suggested that the loss of SAT-1-mediated oxalate secretion by the intestine was responsible for the hyperoxaluria, hyperoxalemia, and calcium oxalate urolithiasis reportedly displayed by this model. To test this hypothesis, we compared the transepithelial fluxes of C-oxalate, , and Cl across isolated, short-circuited segments of the distal ileum, cecum, and distal colon from wild-type (WT) and SAT-1-KO mice. Read More

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http://dx.doi.org/10.1152/ajpgi.00299.2018DOI Listing
January 2019
3 Reads

Acute administration of IL-6 improves indices of hepatic glucose and insulin homeostasis in lean and obese mice.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 1;316(1):G166-G178. Epub 2018 Nov 1.

Department of Human Health and Nutritional Sciences, University of Guelph , Guelph, Ontario , Canada.

Obesity can lead to impairments in hepatic glucose and insulin homeostasis, and although exercise is an effective treatment, the molecular targets remain incompletely understood. As IL-6 is an exercise-inducible cytokine, we aimed to identify whether IL-6 itself influences hepatic glucose and insulin homeostasis and whether this response differs during obesity. In vivo, male mice were fed a low-fat diet (LFD; 10% kcal) or a high-fat diet (HFD; 60% kcal) for 7 wk, which induced obesity and hepatic lipid accumulation. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00097.2018
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http://dx.doi.org/10.1152/ajpgi.00097.2018DOI Listing
January 2019
3 Reads

Asymmetric cell division-dominant neutral drift model for normal intestinal stem cell homeostasis.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 25;316(1):G64-G74. Epub 2018 Oct 25.

Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland.

The normal intestinal epithelium is continuously regenerated at a rapid rate from actively cycling Lgr5-expressing intestinal stem cells (ISCs) that reside at the crypt base. Recent mathematical modeling based on several lineage-tracing studies in mice shows that the symmetric cell division-dominant neutral drift model fits well with the observed in vivo growth of ISC clones and suggests that symmetric divisions are central to ISC homeostasis. However, other studies suggest a critical role for asymmetric cell division in the maintenance of ISC homeostasis in vivo. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00242.2018
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http://dx.doi.org/10.1152/ajpgi.00242.2018DOI Listing
January 2019
7 Reads

5-HT receptor signaling in serotonin transporter-knockout rats: a female sex-specific animal model of visceral hypersensitivity.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 25;316(1):G132-G143. Epub 2018 Oct 25.

Department of Pharmacology and Toxicology, Michigan State University , East Lansing, Michigan.

The irritable bowel syndrome (IBS) is a functional gastrointestinal motor and visceral sensation disorder that is more common in women than men. Female serotonin transporter (SERT)-gene knockout (KO) rats exhibit hypersensitivity to colorectal balloon distention (CRD) that mimics colonic hypersensitivity occurring in female IBS patients. Alosetron (5-HT receptor antagonist) is used to treat diarrhea-predominant IBS in female patients. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00131.2018
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http://dx.doi.org/10.1152/ajpgi.00131.2018DOI Listing
January 2019
6 Reads