5,186 results match your criteria American journal of physiology. Gastrointestinal and liver physiology[Journal]


Inhibition of LXR Signaling by SULT2B1b Promotes Liver Regeneration After Partial Hepatectomy in Mouse Models of Nonalcoholic Fatty Liver Disease.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 1. Epub 2020 Jun 1.

The department of pathology, Fudan University, China.

Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) plays a critical role in hepatic energy homeostasis. Liver X receptors (LXRs) are implicated in multiple physiological functions, including the inhibition of hepatocyte proliferation and regulation of fatty acid and cholesterol metabolism. We have previously reported that SULT2B1b promotes hepatocyte proliferation by inactivating LXR signaling in vivo and in vitro, leading to our hypothesis that SULT2B1b promotes fatty liver regeneration. Read More

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http://dx.doi.org/10.1152/ajpgi.00380.2019DOI Listing

Acetylcholine Exerts Inhibitory and Excitatory Actions on Mouse Ileal Pacemaker Activity: The Role of Muscarinic versus Nicotinic Receptors.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 1. Epub 2020 Jun 1.

School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.

The effect of acetylcholine (ACh) on pacemaking and spontaneous contractions in the gastrointestinal tract is not well-characterized. The current study aims to profile the effect of several muscarinic and nicotinic receptor agonists and antagonists on pacemaker potentials in the ICR mouse ileum. Pacemaker potentials of whole-thickness mouse ileal segments were recorded extracellularly using a 60-channel microelectrode array (MEA) platform. Read More

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http://dx.doi.org/10.1152/ajpgi.00003.2020DOI Listing

Alterations in Pancreatic Islet Cell Function in Response to Small Bowel Resection.

Am J Physiol Gastrointest Liver Physiol 2020 May 28. Epub 2020 May 28.

Pediatric Surgery, St. Louis Children's Hospital, United States.

Background - After massive small bowel resection (SBR), mice exhibit hepatic steatosis, impaired glucose metabolism without insulin resistance, and increased pancreatic islet area. We sought to determine the consequences of SBR on pancreatic b-cell morphology, proliferation, and expression of a key regulatory hormone, glucagon like peptide-1 (GLP-1). Methods - C57Bl/6 mice underwent 50% SBR or sham operation. Read More

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http://dx.doi.org/10.1152/ajpgi.00282.2019DOI Listing

Lipid droplets disrupt mechanosensing in human hepatocytes.

Am J Physiol Gastrointest Liver Physiol 2020 May 28. Epub 2020 May 28.

905 BRB, University of Pennsylvania School of Medicine, United States.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and stiffness is a significant risk factor, HCC can also arise in non-cirrhotic livers in the setting of non-alcoholic fatty liver disease (NAFLD). We hypothesized that lipid droplets in NAFLD might apply mechanical forces to the nucleus, functioning as mechanical stressors akin to stiffness. Read More

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http://dx.doi.org/10.1152/ajpgi.00098.2020DOI Listing

microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3.

Am J Physiol Gastrointest Liver Physiol 2020 May 28. Epub 2020 May 28.

Department of Hematology and Oncology, The Second Hospital of Jilin University, China.

Pancreatic cancer (PC) is a lethal cancer in the digestive system. microRNAs (miRNAs) have been demonstrated to participate in PC progression. In this context, we thus aimed to explore the mechanism of miR-382 in epithelial mesenchymal transition (EMT) and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. Read More

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http://dx.doi.org/10.1152/ajpgi.00322.2019DOI Listing

CORRIGENDUM.

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Am J Physiol Gastrointest Liver Physiol 2020 Jun;318(6):G1054

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http://dx.doi.org/10.1152/ajpgi.zh3-7794corr.2020DOI Listing

Microbial Metabolite Indole-3-Propionic Acid Supplementation Does Not Protect Mice from the Cardiometabolic Consequences of a Western Diet.

Am J Physiol Gastrointest Liver Physiol 2020 May 18. Epub 2020 May 18.

Food Science and Human Nutrition, Colorado State University, United States.

Emerging evidence suggests that intestinal microbes regulate host physiology and cardiometabolic health, although the mechanism(s) by which they do so are unclear. Indoles are a group of compounds produced from bacterial metabolism of the amino acid tryptophan. In light of recent data suggesting broad physiological effects of indoles on host physiology, we examined whether indole-3-propionic acid (IPA) would protect mice from the cardiometabolic consequences of a western diet. Read More

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http://dx.doi.org/10.1152/ajpgi.00375.2019DOI Listing

Cellular maps of gastrointestinal organs: getting the most from tissue clearing.

Am J Physiol Gastrointest Liver Physiol 2020 May 18. Epub 2020 May 18.

Departments of Pediatrics and Biochemistry & Molecular Biology, University of Southern California and Children's Hospital Los Angeles, United States.

The development of modern methods to induce optical transparency ("clearing") in biological tissues has enabled the 3d reconstruction of intact organs at cellular resolution. New capabilities in visualization of rare cellular events, long-range interactions, and irregular structures will facilitate novel studies in the alimentary tract and gastrointestinal systems. The tubular geometry of the alimentary tract facilitates large-scale cellular reconstruction of cleared tissue without specialized microscopy setups. Read More

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http://dx.doi.org/10.1152/ajpgi.00075.2020DOI Listing

Glucagon like peptide 1 and glucose-dependent insulinotropic polypeptide stimulate the release of substance P from TRPV1 and TRPA1 expressing sensory nerves.

Am J Physiol Gastrointest Liver Physiol 2020 May 18. Epub 2020 May 18.

Nutritional Sciences and Toxicology, University of California at Berkeley, United States.

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells (EEC) in response to nutrient ingestion and lowers blood glucose levels by stimulation of insulin secretion, and thus are defined as incretins. GLP-1 receptor (GLP-1R) expression has been identified on enteric neurons that include intrinsic afferent neurons, extrinsic spinal and vagal sensory afferents, but has not been shown to have an incretin effect through these nerves. GLP-1 and GIP enter the mesenteric lymphatic fluid (MLF) after a meal via the interstitial fluid (IF) from local tissue secretion and/or blood capillaries. Read More

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http://dx.doi.org/10.1152/ajpgi.00189.2019DOI Listing

Antibiotic exposure postweaning disrupts the neurochemistry and function of enteric neurons mediating colonic motor activity.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 11;318(6):G1042-G1053. Epub 2020 May 11.

Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.

The period during and immediately after weaning is an important developmental window when marked shifts in gut microbiota can regulate the maturation of the enteric nervous system (ENS). Because microbiota-derived signals that modulate ENS development are poorly understood, we examined the physiological impact of the broad spectrum of antibiotic, vancomycin-administered postweaning on colonic motility, neurochemistry of enteric neurons, and neuronal excitability. The functional impact of vancomycin on enteric neurons was investigated by Ca imaging in reporter mice to characterize alterations in the submucosal and the myenteric plexus, which contains the neuronal circuitry controlling gut motility. Read More

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http://dx.doi.org/10.1152/ajpgi.00088.2020DOI Listing

Lipopolysaccharides (LPS) transport during fat absorption in rodent small intestine.

Am J Physiol Gastrointest Liver Physiol 2020 May 11. Epub 2020 May 11.

University of California Los Angeles.

Lipopolysaccharides (LPS) are potent pro-inflammatory molecules that enter the systemic circulation from the intestinal lumen by uncertain mechanisms. We investigated these mechanisms and the effect of exogenous glucagon-like peptide-2 (GLP-2) on LPS transport in rodent small intestine. Transmucosal LPS transport was measured in Ussing-chambered rat jejunal mucosa. Read More

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http://dx.doi.org/10.1152/ajpgi.00079.2020DOI Listing

CORRIGENDUM.

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Am J Physiol Gastrointest Liver Physiol 2020 May;318(5):G988

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http://dx.doi.org/10.1152/ajpgi.zh3-7785corr.2020DOI Listing

Experimental Analysis of T-Cell Epitopes for Designing Liver Cancer Vaccine Predicted by System Level Immunoinformatics Approach.

Am J Physiol Gastrointest Liver Physiol 2020 May 4. Epub 2020 May 4.

The First Affiliated Hospital of Wenzhou Medical University.

Liver cancer (LC) is the worldwide disease and currently, due to the poor prognostic and therapeutic options of liver cancer, we investigated the T-cell epitopes as potential therapeutic vaccine candidates to get the benefit of experimental processes and utilize the complete ability of the immune system compared to other artificial ex vivo proliferation of T cells. Activation of T-cells targets and kills several tumors, developing a strong rationale for the improvement of immunotherapeutic strategies to cancer therapy. To predict T-cell epitopes for liver cancer, we designed a comprehensive immunoinformatics framework involving data mining, immunogenicity prediction, functional proteomic analysis, conservation studies, molecular modeling and in vivo validation analysis. Read More

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http://dx.doi.org/10.1152/ajpgi.00068.2020DOI Listing
May 2020
3.798 Impact Factor

Immune modulating effects of additional supplementation of estradiol combined with testosterone in murine testosterone-deficient NAFLD model.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 4;318(6):G989-G999. Epub 2020 May 4.

Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Read More

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http://dx.doi.org/10.1152/ajpgi.00310.2019DOI Listing

HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 27;318(6):G1022-G1033. Epub 2020 Apr 27.

The Hormel Institute, University of Minnesota, Austin, Minnesota.

Reduced ciliary expression is reported in several tumors, including cholangiocarcinoma (CCA). We previously showed primary cilia have tumor suppressor characteristics, and HDAC6 is involved in ciliary loss. However, mechanisms of ciliary disassembly are unknown. Read More

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http://dx.doi.org/10.1152/ajpgi.00033.2020DOI Listing

Letter to Editor: Takeda-G protein receptor-5 signaling mitigates parenteral nutrition-associated liver disease: public health impact.

Authors:
Saumya Pandey

Am J Physiol Gastrointest Liver Physiol 2020 May;318(5):G928-G929

Department of Clinical Research, Indira-IVF Hospital, Udaipur, India.

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http://dx.doi.org/10.1152/ajpgi.00073.2020DOI Listing

Reply to "Letter to Editor: Takeda-G Protein Receptor-5 signaling mitigates parenteral nutrition-associated liver disease: public health impact".

Authors:
Joseph F Pierre

Am J Physiol Gastrointest Liver Physiol 2020 May;318(5):G930

Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.

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http://dx.doi.org/10.1152/ajpgi.00080.2020DOI Listing

Dopamine D2 receptor activator quinpirole protects against trypsinogen activation during acute pancreatitis via upregulating HSP70.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 20;318(6):G1000-G1012. Epub 2020 Apr 20.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Trypsinogen activation is the hallmark of acute pancreatitis (AP) independent of intra-acinar NF-κB activation and inflammation. We previously found that dopamine (DA) receptor 2 (DRD2) activation controls inflammation during AP via PP2A-dependent NF-κB activation. In this study, we sought to examine whether DRD2 signaling mediates trypsinogen activation and the underlying mechanisms. Read More

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http://dx.doi.org/10.1152/ajpgi.00354.2019DOI Listing
June 2020
3.798 Impact Factor

Microbiota-neuroimmune cross talk in stress-induced visceral hypersensitivity of the bowel.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 20;318(6):G1034-G1041. Epub 2020 Apr 20.

Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Visceral hypersensitivity of the lower gastrointestinal tract, defined as an increased response to colorectal distension, frequently prompts episodes of debilitating abdominal pain in irritable bowel syndrome (IBS). Although the pathophysiology of IBS is not yet fully elucidated, it is well known that stress is a major risk factor for development and acts as a trigger of pain sensation. Stress modulates both immune responses as well as the gut microbiota and vice versa. Read More

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http://dx.doi.org/10.1152/ajpgi.00196.2019DOI Listing

Pharmacological activation of TGR5 promotes intestinal growth via a GLP-2-dependent pathway in mice.

Am J Physiol Gastrointest Liver Physiol 2020 May 20;318(5):G980-G987. Epub 2020 Apr 20.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Glucagon-like peptide (GLP)-1 and -2-secreting L cells have been shown to express the bile acid receptor Takeda G protein-receptor-5 (TGR5) and increase secretion upon receptor activation. Previous studies have explored GLP-1 secretion following acute TGR5 activation, but chronic activation and GLP-2 responses have not been characterized. In this study, we aimed to investigate the consequences of pharmacological TGR5 receptor activation on L cell hormone production in vivo using the specific TGR5 agonist RO5527239 and the GLP-2 receptor knockout mouse. Read More

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http://dx.doi.org/10.1152/ajpgi.00062.2020DOI Listing

Gut leakage enhances sepsis susceptibility in iron-overloaded β-thalassemia mice through macrophage hyperinflammatory responses.

Am J Physiol Gastrointest Liver Physiol 2020 May 20;318(5):G966-G979. Epub 2020 Apr 20.

Faculty of Medicine, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.

Iron overload induces intestinal-permeability defect (gut leakage), and gut translocation of organismal molecules might enhance systemic inflammation and sepsis severity in patients with thalassemia (Thal). Hence, iron administration in Hbb mice, heterozygous β-globin-deficient Thal mice, was explored. Oral iron administration induced more severe secondary hemochromatosis and gut leakage in Thal mice compared with wild-type (WT) mice. Read More

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http://dx.doi.org/10.1152/ajpgi.00337.2019DOI Listing

Changes in specific esophageal neuromechanical wall states are associated with conscious awareness of a solid swallowed bolus in healthy subjects.

Am J Physiol Gastrointest Liver Physiol 2020 May 13;318(5):G946-G954. Epub 2020 Apr 13.

Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.

Esophageal neuromechanical wall states are the physical manifestations of circular muscle inhibition and contraction resulting from neural inputs and leading to bolus propulsion. A novel method infers esophageal neuromechanical wall states through simultaneous determination of pressure and diameter in vivo using impedance manometry. We hypothesized that changes in esophageal neuromechanical wall states relate to conscious awareness of esophageal bolus passage ("bolus perception"). Read More

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http://dx.doi.org/10.1152/ajpgi.00235.2019DOI Listing

Mechanical roles of anterograde and retrograde intestinal peristalses after feeding in a larval fish ().

Am J Physiol Gastrointest Liver Physiol 2020 Jun 13;318(6):G1013-G1021. Epub 2020 Apr 13.

Department of Finemechanics, Graduate School of Engineering, Tohoku University, Sendai, Japan.

Transport in gut is important, not only for digestion, metabolism, and nutrient uptake, but also for microbiotic circumstance in the digestive tract; however, the effects of mixing and pumping in the intestine have not been fully clarified. Therefore, in this study, we quantitatively explored intestinal mixing and pumping, represented using a dispersion coefficient and pressure rise in zebrafish larvae, which is a model organism for vertebrate digestive studies, over time by measuring transport phenomena after feeding. Here we provide the first quantitative evidence of the roles of anterograde and retrograde intestinal peristalses in the larval fish of after feeding in terms of digestive pumping and mixing functions by an in vivo imaging of intestinal propagation waves in the larval intestine. Read More

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http://dx.doi.org/10.1152/ajpgi.00165.2019DOI Listing

Small molecules, big effects: microbial metabolites in intestinal immunity.

Am J Physiol Gastrointest Liver Physiol 2020 May 6;318(5):G907-G911. Epub 2020 Apr 6.

Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania.

The mammalian intestine is host to a vast number of microbial organisms. The immune system must balance tolerance with innate and adaptive defense mechanisms to maintain homeostasis with the microbial community. Interestingly, microbial metabolites have been shown to play a role in shaping the host immune response, thus assisting with adaptations that have significant implications for human health and disease. Read More

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http://dx.doi.org/10.1152/ajpgi.00263.2019DOI Listing

Human intestinal enteroids as a model of -induced enteritis.

Am J Physiol Gastrointest Liver Physiol 2020 May 30;318(5):G870-G888. Epub 2020 Mar 30.

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

is an important nosocomial pathogen that produces toxins to cause life-threatening diarrhea and colitis. Toxins bind to epithelial receptors and promote the collapse of the actin cytoskeleton. toxin activity is commonly studied in cancer-derived and immortalized cell lines. Read More

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http://dx.doi.org/10.1152/ajpgi.00045.2020DOI Listing

Fermentable fibers induce rapid macro- and micronutrient depletion in Toll-like receptor 5-deficient mice.

Am J Physiol Gastrointest Liver Physiol 2020 May 23;318(5):G955-G965. Epub 2020 Mar 23.

Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.

Functional fermentable fibers are considered essential for a healthy diet. Recently, we demonstrated that gut microbiota dysbiotic mice fed an inulin-containing diet (ICD) developed hepatocellular carcinoma (HCC) within 6 mo. In particular, a subset of Toll-like receptor 5-deficient (T5KO) mice prone to HCC exhibited rapid onset of hyperbilirubinemia (HB) and cholemia; these symptoms provide rationale that ICD induces cholestasis. Read More

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http://dx.doi.org/10.1152/ajpgi.00349.2019DOI Listing
May 2020
3.798 Impact Factor

infection impairs chaperone-assisted maturation of Na-K-ATPase in gastric epithelium.

Am J Physiol Gastrointest Liver Physiol 2020 May 16;318(5):G931-G945. Epub 2020 Mar 16.

Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California.

infection always induces gastritis, which may progress to ulcer disease or cancer. The mechanisms underlying mucosal injury by the bacteria are incompletely understood. Here, we identify a novel pathway for -induced gastric injury, the impairment of maturation of the essential transport enzyme and cell adhesion molecule, Na-K-ATPase. Read More

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http://dx.doi.org/10.1152/ajpgi.00266.2019DOI Listing

When physiology meets technology: redefining colonic mass movements.

Authors:
Gabrio Bassotti

Am J Physiol Gastrointest Liver Physiol 2020 Apr 16;318(4):G793-G795. Epub 2020 Mar 16.

Gastroenterology, Hepatology, and Digestive Endoscopy Section, Department of Medicine, University of Perugia Medical School; Gastroenterology Section, Perugia General Hospital, Perugia, Italy.

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http://dx.doi.org/10.1152/ajpgi.00066.2020DOI Listing

miR-524-5p inhibits angiogenesis through targeting WNK1 in colon cancer cells.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 16;318(4):G827-G839. Epub 2020 Mar 16.

Department of Ultrasound, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang, People's Republic of China.

There is increasing evidence that microRNA (miRNA) abnormity is involved in the occurrence and the development of various malignancies, including colon cancer. MiRNA-524-5p has been reported to possess anticancer activity in various tumors, which function is seldom investigated in colon cancer cells. The aim of this study was to explore the effect of the miRNA-524-5p/with-no-lysine kinase 1 (WNK1) system on angiogenesis in a colon cancer cell line (HT-29 and COLO205 cells) and further investigate the potential mechanisms. Read More

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http://dx.doi.org/10.1152/ajpgi.00369.2019DOI Listing

Glucagon receptor signaling is not required for -carbamoyl glutamate- and l-citrulline-induced ureagenesis in mice.

Am J Physiol Gastrointest Liver Physiol 2020 May 16;318(5):G912-G927. Epub 2020 Mar 16.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Glucagon regulates the hepatic amino acid metabolism and increases ureagenesis. Ureagenesis is activated by -acetylglutamate (NAG), formed via activation of -acetylglutamate synthase (NAGS). With the aim to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we investigated whether glucagon receptor-mediated activation of ureagenesis is required in a situation where NAGS activity and/or NAG levels are sufficient to activate the first step of the urea cycle in vivo. Read More

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http://dx.doi.org/10.1152/ajpgi.00294.2019DOI Listing

CORRIGENDUM.

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Am J Physiol Gastrointest Liver Physiol 2020 Mar;318(3):G610-G611

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http://dx.doi.org/10.1152/ajpGI.zh3-7745-corr.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099498PMC

A story of liver and gut microbes: how does the intestinal flora affect liver disease? A review of the literature.

Am J Physiol Gastrointest Liver Physiol 2020 May 9;318(5):G889-G906. Epub 2020 Mar 9.

Dipartimento Universitario Clinico di Scienze Mediche Chirurgiche e della Salute, Università degli Studi di Trieste, Italy.

Each individual is endowed with a unique gut microbiota (GM) footprint that mediates numerous host-related physiological functions, such as nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. Because of increased scientific interest in the GM, its central role in the pathophysiology of many intestinal and extraintestinal conditions has been recognized. Given the close relationship between the gastrointestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. Read More

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http://dx.doi.org/10.1152/ajpgi.00161.2019DOI Listing

negatively regulates the epithelial-to-mesenchymal transition in colorectal cancer through the Wnt signaling pathway.

Am J Physiol Gastrointest Liver Physiol 2020 May 9;318(5):G841-G853. Epub 2020 Mar 9.

Department of Gastrointestinal Surgery, Ruian People's Hospital, Ruian, Zhejiang, China.

Colorectal cancer (CRC) is one of the most common malignant tumors and is associated with a high mortality rate due to the lack of specific biomarkers available for early diagnosis, targeted therapies, and prognostic surveillance. In the present study, we investigated the function of and its underlying mechanism in CRC. Immunohistochemical staining and clinicopathological analysis were used to assess the expression of and its clinical significance in patients with CRC. Read More

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http://dx.doi.org/10.1152/ajpgi.00178.2019DOI Listing

Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 9;318(4):G816-G826. Epub 2020 Mar 9.

APC Microbiome Ireland, University College Cork, Cork, Ireland.

The gastrointestinal tract houses a reservoir of bacterial-derived enzymes that can directly catalyze the metabolism of drugs, dietary elements and endogenous molecules. Both host and environmental factors may influence this enzymatic activity, with the potential to dictate the availability of the biologically-active form of endogenous molecules in the gut and influence inter-individual variation in drug metabolism. We aimed to investigate the influence of the microbiota, and the modulation of its composition, on fecal enzymatic activity. Read More

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http://dx.doi.org/10.1152/ajpgi.00026.2020DOI Listing

SNX27 regulates DRA activity and mediates its direct recycling by PDZ-interaction in early endosomes at the apical pole of Caco2 cells.

Am J Physiol Gastrointest Liver Physiol 2020 May 2;318(5):G854-G869. Epub 2020 Mar 2.

Department of Gastroenterology and Endocrinology, Center for Internal Medicine, Rostock University Medical Center, Rostock, Germany.

DRA (downregulated in adenoma, SLC26A3) and NHE3 (Na/H exchanger 3, SLC9A3) together mediate intestinal electroneutral NaCl absorption. Both transporters contain PDZ (postsynaptic density 95, disc large, zonula occludens 1) binding motifs and interact with PDZ adaptor proteins regulating their activity and recycling. SNX27 (sorting nexin 27) contains a PDZ domain and is involved in the recycling of cargo proteins including NHE3. Read More

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http://dx.doi.org/10.1152/ajpgi.00374.2019DOI Listing

Ethanol feeding accelerates pancreatitis progression in mutant mice.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 2;318(4):G694-G704. Epub 2020 Mar 2.

Center for Exocrine Disorders, Department of Molecular and Cell Biology, Boston University, Henry M. Goldman School of Dental Medicine, Boston, Massachusetts.

Alcoholic pancreatitis is a multifactorial, progressive, inflammatory disorder of the pancreas. Alcohol initiates pancreatitis and promotes its progression in the context of genetic susceptibility and/or other environmental risk factors such as smoking. Genetic mutations can cause digestive enzyme misfolding, which induces endoplasmic reticulum (ER) stress and elicits pancreatitis. Read More

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http://dx.doi.org/10.1152/ajpgi.00007.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191466PMC

Unraveling the transcriptional determinants of liver sinusoidal endothelial cell specialization.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 2;318(4):G803-G815. Epub 2020 Mar 2.

Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

Liver sinusoidal endothelial cells (LSECs) are the first liver cells to encounter waste macromolecules, pathogens, and toxins in blood. LSECs are highly specialized to mediate the clearance of these substances via endocytic scavenger receptors and are equipped with fenestrae that mediate the passage of macromolecules toward hepatocytes. Although some transcription factors (TFs) are known to play a role in LSEC specialization, information about the specialized LSEC signature and its transcriptional determinants remains incomplete. Read More

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http://dx.doi.org/10.1152/ajpgi.00215.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191457PMC

Perturbed mitochondrial dynamics, an emerging aspect of epithelial-microbe interactions.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 2;318(4):G748-G762. Epub 2020 Mar 2.

Department of Medical Genetics and Biochemistry & Molecular Biology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

Mitochondria exist in a complex network that is constantly remodeling via the processes of fission and fusion in response to intracellular conditions and extracellular stimuli. Excessive fragmentation of the mitochondrial network because of an imbalance between fission and fusion reduces the cells' capacity to generate ATP and can be a forerunner to cell death. Given the critical roles mitochondria play in cellular homeostasis and innate immunity, it is not surprising that many microbial pathogens can disrupt mitochondrial activity. Read More

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http://dx.doi.org/10.1152/ajpgi.00031.2020DOI Listing

ROCK1 inhibitor stabilizes E-cadherin and improves barrier function in experimental necrotizing enterocolitis.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 24;318(4):G781-G792. Epub 2020 Feb 24.

Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of newborns. Although incompletely understood, NEC is associated with intestinal barrier dysfunction. E-cadherin, an adherens junction, is a protein complex integral in maintaining normal barrier homeostasis. Read More

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http://dx.doi.org/10.1152/ajpgi.00195.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191467PMC

Severe neonatal anemia increases intestinal permeability by disrupting epithelial adherens junctions.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 24;318(4):G705-G716. Epub 2020 Feb 24.

Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.

Anemia is a frequent diagnosis in critically ill infants, but the clinical implications of severe anemia in these patients remain unclear. In this study, we examined preweaned mice to investigate the effects of severe anemia during early infancy on gut mucosal permeability. C57BL/6 mice were subjected to timed phlebotomy between to induce severe anemia (hematocrits 20%-24%), and intestinal permeability was tracked longitudinally between and as intestine-to-plasma translocation of enteral macromolecules and bacterial translocation. Read More

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http://dx.doi.org/10.1152/ajpgi.00324.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191465PMC

Aging-related liver degeneration is associated with increased bacterial endotoxin and lipopolysaccharide binding protein levels.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 24;318(4):G736-G747. Epub 2020 Feb 24.

Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.

Aging is a risk factor in the development of many diseases, including liver-related diseases. The two aims of the present study were ) to determine how aging affects liver health in mice in the absence of any interventions and ) if degenerations observed in relation to blood endotoxin levels are critical in aging-associated liver degeneration. Endotoxin levels and markers of liver damage, mitochondrial dysfunction, insulin resistance, and apoptosis as well as the Toll-like receptor 4 (Tlr-4) signaling cascade were studied in liver tissue and blood, respectively, of 3- and 24-mo-old male C57BL/6J mice. Read More

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http://dx.doi.org/10.1152/ajpgi.00345.2018DOI Listing

Signaling through the interleukin-4 and interleukin-13 receptor complexes regulates cholangiocyte TMEM16A expression and biliary secretion.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 24;318(4):G763-G771. Epub 2020 Feb 24.

Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

TMEM16A is a Ca-activated Cl channel in the apical membrane of biliary epithelial cells, known as cholangiocytes, which contributes importantly to ductular bile formation. Whereas cholangiocyte TMEM16A activity is regulated by extracellular ATP-binding membrane purinergic receptors, channel expression is regulated by interleukin-4 (IL-4) through an unknown mechanism. Therefore, the aim of the present study was to identify the signaling pathways involved in TMEM16A expression and cholangiocyte secretion. Read More

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http://dx.doi.org/10.1152/ajpgi.00219.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191463PMC

On the nature of high-amplitude propagating pressure waves in the human colon.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 18;318(4):G646-G660. Epub 2020 Feb 18.

McMaster University, Department of Medicine, Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada.

Characterization of high-amplitude propagating pressure waves (HAPWs or HAPCs) plays a key role in diagnosis of colon dysmotility using any type of colonic manometry. With the introduction of high-resolution manometry, more insight is gained into this most prominent propulsive motor pattern. Here, we use a water-perfused catheter with 84 sensors with intervals between measuring points of 1 cm throughout the colon, for 6-8 h, in 19 healthy subjects. Read More

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http://dx.doi.org/10.1152/ajpgi.00386.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191456PMC

Anti-inflammatory effects of sacral nerve stimulation: a novel spinal afferent and vagal efferent pathway.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 18;318(4):G624-G634. Epub 2020 Feb 18.

Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Sacral nerve stimulation (SNS) was reported to improve 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. The aim of this study was to investigate whether the SNS anti-inflammatory effect is mediated via the local sacral splanchnic nerve or the spinal afferent-vagal efferent-colon pathway. Under general anesthesia, rats were administrated with TNBS intrarectally, and bipolar SNS electrodes were implanted unilaterally at S. Read More

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http://dx.doi.org/10.1152/ajpgi.00330.2019DOI Listing
April 2020
3.798 Impact Factor

Organ-specific lymphatics play distinct roles in regulating HDL trafficking and composition.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 18;318(4):G725-G735. Epub 2020 Feb 18.

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.

Recently, peripheral lymphatic vessels were found to transport high-density lipoprotein (HDL) from interstitial tissues to the blood circulation during reverse cholesterol transport. This function is thought to be critical to the clearance of cholesterol from atherosclerotic plaques. The role of organ-specific lymphatics in modulating HDL transport and composition is, however, incompletely understood. Read More

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http://dx.doi.org/10.1152/ajpgi.00340.2019DOI Listing

Responses of gut and pancreatic hormones, bile acids, and fibroblast growth factor-21 differ to glucose, protein, and fat ingestion after gastric bypass surgery.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 18;318(4):G661-G672. Epub 2020 Feb 18.

Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.

Postprandial gut hormone responses change after Roux-en-Y gastric bypass (RYGB), and we investigated the impact of glucose, protein, and fat (with and without pancreas lipase inhibition) on plasma responses of gut and pancreas hormones, bile acids, and fibroblast growth factor 21 (FGF-21) after RYGB and in nonoperated control subjects. In a randomized, crossover study 10 RYGB operated and 8 healthy weight-matched control subjects were administered 4 different 4-h isocaloric (200 kcal) liquid meal tests containing >90 energy (E)% of either glucose, protein (whey protein), or fat (butter with and without orlistat). The primary outcome was glucagon-like peptide-1 (GLP-1) secretion (area under the curve above baseline). Read More

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http://dx.doi.org/10.1152/ajpgi.00265.2019DOI Listing

The microbiome-adipose tissue axis in systemic metabolism.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 18;318(4):G717-G724. Epub 2020 Feb 18.

Microbiology Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

The intestinal commensal microbiome is an important component of host health, in part by contributing an abundance of metabolites that gain access to the systemic circulation. The microbiome thereby influences the physiology of numerous organ systems outside the gastrointestinal tract. The consequences of this signaling axis between the intestinal microbiome and host are profound, in particular for the modulation of organismal metabolism. Read More

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http://dx.doi.org/10.1152/ajpgi.00304.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191461PMC

Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 18;318(4):G613-G623. Epub 2020 Feb 18.

Center for Gastrointestinal Biology and Disease, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.

Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Read More

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http://dx.doi.org/10.1152/ajpgi.00086.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191458PMC

Secretin effects on gastric functions, hormones and symptoms in functional dyspepsia and health: randomized crossover trial.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 10;318(4):G635-G645. Epub 2020 Feb 10.

Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Abnormal gastric accommodation (GA) and gastric emptying contribute to pathophysiology in functional dyspepsia (FD). Secretin is a key regulator of GA in animal studies. Our aim was to study the effects of secretin on gastric motility, satiation, postprandial symptoms, and key hormones. Read More

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http://dx.doi.org/10.1152/ajpgi.00371.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191464PMC

Intestine-specific deletion of metal transporter causes brain manganese overload and locomotor defects of manganism.

Am J Physiol Gastrointest Liver Physiol 2020 Apr 31;318(4):G673-G681. Epub 2020 Jan 31.

Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida.

Impaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Read More

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http://dx.doi.org/10.1152/ajpgi.00301.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191460PMC