Adaptive regulation of pancreatic acinar mitochondrial thiamin pyrophosphate uptake process: possible involvement of epigenetic mechanism(s)
The essentiality of thiamin stems from its roles as a cofactor [mainly in the form of thiamin pyrophosphate (TPP)] in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known abou...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Sabui, S., Subramanian, V. S., Kapadia, R., Said, H. M. Tags: RESEARCH ARTICLE Source Type: research

Relationship of gastric emptying or accommodation with satiation, satiety, and postprandial symptoms in health
The contributions of gastric emptying (GE) and gastric accommodation (GA) to satiation, satiety, and postprandial symptoms remain unclear. We aimed to evaluate the relationships between GA or GE with satiation, satiety, and postprandial symptoms in healthy overweight or obese volunteers (total n = 285, 73% women, mean BMI 33.5 kg/m2): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing. We assessed GE of solids, gastric volumes, calorie intake at buffet meal, and satiation by measuring volume to comfortable fullness (VTF) and maximum tolerated volume (MTV...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Halawi, H., Camilleri, M., Acosta, A., Vazquez-Roque, M., Oduyebo, I., Burton, D., Busciglio, I., Zinsmeister, A. R. Tags: RESEARCH ARTICLE Source Type: research

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat
Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1) assess the gastric effects of brain stem DA application, 2) identify the DA receptor subtype, and, 3) ident...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Anselmi, L., Toti, L., Bove, C., Travagli, R. A. Tags: RESEARCH ARTICLE Source Type: research

Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal
Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα+) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in KitW/KitW-v (W/Wv) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Durnin, L., Lees, A., Manzoor, S., Sasse, K. C., Sanders, K. M., Mutafova-Yambolieva, V. N. Tags: RESEARCH ARTICLE Source Type: research

Melatonin inhibits hypothalamic gonadotropin-releasing hormone release and reduces biliary hyperplasia and fibrosis in cholestatic rats
This study expands these findings by investigating neural GnRH regulation by melatonin during BDL-induced cholestasis by infusing melatonin into the brain. Melatonin infusion reduced cholangiocyte proliferation and fibrosis, and these effects are due to GNRH receptor 1-dependent paracrine signaling between cholangiocytes and hepatic stellate cells. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: McMillin, M., DeMorrow, S., Glaser, S., Venter, J., Kyritsi, K., Zhou, T., Grant, S., Giang, T., Greene, J. F., Wu, N., Jefferson, B., Meng, F., Alpini, G. Tags: RESEARCH ARTICLE Source Type: research

PARP2 deficiency affects invariant-NKT-cell maturation and protects mice from concanavalin A-induced liver injury
In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis. NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Filliol, A., Piquet-Pellorce, C., Dion, S., Genet, V., Lucas-Clerc, C., Dantzer, F., Samson, M. Tags: RESEARCH ARTICLE Source Type: research

Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis
Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology that may also affect the liver, causes a great deal of morbidity and mortality in premature infants. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of intestinal and hepatic damage in an established murine NEC model. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would exacerbate experimental NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose it. Genetic deletion of the 5-HT transpor...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Gross Margolis, K., Vittorio, J., Talavera, M., Gluck, K., Li, Z., Iuga, A., Stevanovic, K., Saurman, V., Israelyan, N., Welch, M. G., Gershon, M. D. Tags: RESEARCH ARTICLE Source Type: research

Overactivation of intestinal sterol response element-binding protein 2 promotes diet-induced nonalcoholic steatohepatitis
Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver that may progress to hepatic fibrosis and nonalcoholic steatohepatitis (NASH). Mechanisms underlying NAFLD and NASH are not yet fully understood. Dietary cholesterol was recently shown to be a risk factor for the development of NASH, suggesting a role for intestinal handling of cholesterol. One important regulator of cholesterol homeostasis is the sterol response element-binding protein-2 (SREBP-2) transcription factor. We tested the hypothesis that the overactivation of intestinal SREBP-2 increases the susceptibility to diet-induc...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Malhotra, P., Aloman, C., Ankireddy, A., Khadra, H., Ooka, K., Gill, R. K., Saksena, S., Dudeja, P. K., Alrefai, W. A. Tags: RESEARCH ARTICLE Source Type: research

Impact of prevailing thiamin levels on thiamin pyrophosphate uptake in pancreatic acinar cells: do the shuttle!
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Kennedy, L., Francis, H., Alpini, G. Tags: EDITORIAL FOCUS Source Type: research

Role of G protein-coupled receptors-microRNA interactions in gastrointestinal pathophysiology
G protein-coupled receptors (GPCRs) make up the largest transmembrane receptor superfamily in the human genome and are expressed in nearly all gastrointestinal cell types. Coupling of GPCRs and their respective ligands activates various phosphotransferases in the cytoplasm, and, thus, activation of GPCR signaling in intestine regulates many cellular and physiological processes. Studies in microRNAs (miRNAs) demonstrate that they represent critical epigenetic regulators of different pathophysiological responses in different organs and cell types in humans and animals. Here, we reviewed recent research on GPCR-miRNA interact...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2017 Category: Gastroenterology Authors: Law, I. K. M., Padua, D. M., Iliopoulos, D., Pothoulakis, C. Tags: REVIEW Source Type: research

Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice
High-iron feeding of rodents has been commonly used to model human iron-overload disorders. We recently noted that high-iron consumption impaired growth and caused severe systemic copper deficiency in growing rats, but the mechanism by which this occurred could not be determined due to technical limitations. In the current investigation, we thus utilized mice; first to determine if the same phenomenon occurred in another mammalian species, and second since we could assess in vivo copper absorption in mice. We hypothesized that excessive dietary iron impaired intestinal copper absorption. Weanling, male mice were thus fed A...
Source: AJP: Gastrointestinal and Liver Physiology - October 1, 2017 Category: Gastroenterology Authors: Ha, J.-H., Doguer, C., Collins, J. F. Tags: RESEARCH ARTICLE Source Type: research

Validation and characterization of a novel method for selective vagal deafferentation of the gut
We report that CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice also abolishes CCK-induced satiation. Therefore, we provide multiple lines of evidence that injection of CCK-SAP in NG is a novel selective vagal deafferentation technique of the upper GI tract that works in multiple vertebrate ...
Source: AJP: Gastrointestinal and Liver Physiology - October 1, 2017 Category: Gastroenterology Authors: Diepenbroek, C., Quinn, D., Stephens, R., Zollinger, B., Anderson, S., Pan, A., de Lartigue, G. Tags: RESEARCH ARTICLE Source Type: research

Augmentation of cGMP/PKG pathway and colonic motility by hydrogen sulfide
Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cyclic guanosine 5'-monophosphate (cGMP). The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse, and human, l-cysteine, substrate of cystathionine--lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser1756 (measured as a proxy for PKG activation), and muscle relaxa...
Source: AJP: Gastrointestinal and Liver Physiology - October 1, 2017 Category: Gastroenterology Authors: Nalli, A. D., Bhattacharya, S., Wang, H., Kendig, D. M., Grider, J. R., Murthy, K. S. Tags: RESEARCH ARTICLE Source Type: research

Abdominal surgery induced gastric ileus and activation of M1-like macrophages in the gastric myenteric plexus: prevention by central vagal activation in rats
Inflammation plays a role in abdominal surgery (AS)-induced intestinal ileus that is alleviated by electrical vagal stimulation. Intracisternal injection of RX-77368, the stable thyrotropin-releasing hormone agonist, activates dorsal motor nucleus neurons and gastric vagal efferent discharges. We investigated the gastric inflammation induced by AS and the modulation by intracisternal RX-77368 in rats. RX-77368 (50 ng/rat) or saline was injected followed, 1 h later, by laparotomy and small intestinal/cecal manipulation. The sham group had anesthesia alone. After 6 h, gastric emptying (GE) and the inflammation in gastric cor...
Source: AJP: Gastrointestinal and Liver Physiology - October 1, 2017 Category: Gastroenterology Authors: Yuan, P.-Q., Tache, Y. Tags: RESEARCH ARTICLE Source Type: research

Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?
Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 g of remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and posthepatectomy liver failure has been postulated but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/...
Source: AJP: Gastrointestinal and Liver Physiology - October 1, 2017 Category: Gastroenterology Authors: Golriz, M., Abbasi, S., Fathi, P., Majlesara, A., Brenner, T., Mehrabi, A. Tags: RESEARCH ARTICLE Source Type: research