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• W2078604556 abstract "Ingestion of food simultaneously activates gastrointestinal motility, gastric and pancreatic secretion, and release of gastrointestinal hormones that, in turn, modulate motor, secretory, and absorptive functions in the upper gut. The hormones involved in these integrated functions include gastrin, cholecystokinin (CCK), ghrelin, and pancreatic polypeptide from the upper gut and incretins, such as glucagon-like peptide (GLP)-1 and peptide YY (PYY), from the distal small intestine. The responses to ingestion of food are complex and have been traditionally considered in 3 phases: cephalic, gastric, and intestinal. While this allows the different functions to be reduced to manageable descriptions, it is important to note that this is an integrated process with overlap between the different phases. Variations in function result in part from the physical properties of meals, the different proportions of macronutrients, and the rate of emptying from the stomach. In contrast, the enormous functional reserve of the pancreas results in a fairly standard response, influenced mainly by the rate of delivery of nutrients to the duodenum and the nature of nutrients that stimulate the release of enteropancreatic hormones. The ingestion of food leads eventually to a sensation of fullness and cessation of food intake. In this report, the term “satiation” refers to the sensation of fullness developed during the end of meal ingestion or during the early postprandial period. Operationally, this is investigated by the maximum tolerated volume of a nutrient drink ingested at a standard rate and the symptoms 30 minutes postchallenge. On the other hand, satiety refers to the appetite level that is manifested by the timing of the subsequent meal and the number of calories ingested. This is measured in practice by means of ad libitum buffet meals in which the calories and types of nutrients preferred from standard meals are calculated. In this initial phase, cholinergic neural input is the dominant mediator; CCK and gastrin are additional stimulatory modulators. Gustatory and other visceral afferent inputs project into different subnuclei of the nucleus of the solitary tract. Central cholinergic circuits, neuropeptide Y (NPY), and thyrotropin-releasing hormone are candidate central stimulators of the cephalic phase, which is mediated, at least in part, through efferent vagal fibers.1Katschinski M. Nutritional implications of cephalic phase gastrointestinal responses.Appetite. 2000; 34: 189-196Crossref PubMed Scopus (37) Google Scholar Preganglionic motor neurons from vagal subnuclei originate from the topographically organized vertical column in the dorsal motor nucleus of the vagus in the medulla. These are the efferent arms of vagal reflexes in the cephalic phase. Descending projections from the senses, such as olfaction and vision, and from forebrain areas also modulate the reflex response.2Powley T.L. Vagal circuitry mediating cephalic-phase responses to food.Appetite. 2000; 34: 184-188Crossref PubMed Scopus (44) Google Scholar Cephalically stimulated activities are estimated to contribute >50% of the overall secretory postprandial responses and to a significant component of the motor responses to the meal. GLP-1 and PYY provide physiologic inhibition of the cephalic-phase responses as they are released during the intestinal phase of digestion. Modulation of the cephalic phase of digestion may impact postprandial symptoms such as satiation or dyspepsia that influence food intake or may influence the metabolic control such as postprandial glycemia. Vagal function is critical to the postprandial motor, secretory, and sensory responses and their integration. If the gut is a “puppet on a string” controlled by the brain centers, the vagus nerve may legitimately lay claim to being the string! In this section, the mechanisms and physiologic motor responses to food are discussed. Contraction or relaxation of smooth muscle cells and their integration are modulated by extrinsic (the central nervous system and autonomic nerves) and enteric nerves (the enteric nervous system). Extrinsic neural control of upper gastrointestinal motor function consists of the vagal parasympathetic outflow (excitatory to nonsphincteric muscle) and the thoracolumbar sympathetic supply (excitatory to sphincters, inhibitory to nonsphincteric muscle) arising from T5 to T10 of the intermediolateral column of the spinal cord. The prevertebral ganglia integrate afferent impulses between the gut and the central nervous system and provide additional reflex control of the abdominal viscera. The enteric nervous system is an independent nervous system consisting of approximately 100 million neurons organized in ganglionated plexuses. The larger myenteric, or Auerbach’s, plexus is situated between the longitudinal and circular muscle layers of the muscularis externa; it is involved in control of gastrointestinal motility. The submucosal, or Meissner’s, plexus controls absorption, secretion, and mucosal blood flow. Other ganglionated plexuses are not as anatomically defined in different regions of the gut. The enteric nervous system also plays a role in visceral afferent function and in integration of peristalsis. Myogenic factors regulate the electrical activity generated by gastrointestinal smooth muscle cells. Interstitial cells of Cajal form a series of nonneural pacemaker systems in the wall of the gut, at the interface of the circular and longitudinal muscle layers of the stomach and intestine. They function as intermediaries between the enteric nervous system and muscle. Electrical control activity spreads through the contiguous segments of the gut that form muscle syncytia and convey the electrical stimulus through gap junctions and through neurochemical activation. There are excitatory (eg, acetylcholine, substance P) and inhibitory (eg, nitric oxide, somatostatin) transmitters. The unit of motor function in the gut is the peristaltic reflex or the “law of the intestine.” This involves sensation of the luminal stimulus (chemical or mechanical), transduction of the sensation through intrinsic primary afferent neurons, and an integrated excitatory response above and relaxatory response below the site of distention. Interneurons (eg, opioid or somatostatin) coordinate these functions. There are distinct patterns of motor activity in the fasting and postprandial periods (Figure 1).3Coulie B. Camilleri M. Intestinal pseudo-obstruction.Annu Rev Med. 1999; 50: 37-55Crossref PubMed Scopus (63) Google Scholar The fasting period is characterized by the interdigestive migrating motor complex (MMC), a cyclical contraction sequence of average duration of approximately 7 minutes that sweeps through the stomach and small intestine on average about every 90 minutes during fasting in healthy people. With ingestion of a meal, the proximal stomach accommodates food by reduction of its tone,4Thumshirn M. Camilleri M. Saslow S.B. Williams D.E. Burton D.D. Hanson R.B. Gastric accommodation in nonulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function.Gut. 1999; 44: 55-64Crossref PubMed Google Scholar and there is an increase in proximal and distal stomach volume5Kuiken S.D. Samsom M. Camilleri M. Mullan B.P. Burton D.D. Kost L.J. Hardyman T.J. O’Connor M.K. Development of a test to measure gastric accommodation in humans.Am J Physiol. 1999; 277: G1217-G1221PubMed Google Scholar, 6Bouras E.P. Delgado-Aros S. Camilleri M. Castillo E.J. Burton D.D. Thomforde G.M. Chial H.J. SPECT imaging of the stomach comparison with barostat and effects of sex, age, body mass index, and fundoplication.Gut. 2002; 51: 781-786Crossref PubMed Scopus (110) Google Scholar facilitating the ingestion of food without an increase in pressure (Figure 2). This reflex is vagally mediated and involves an intrinsic nitrergic (inhibitory) neuron. In the regions in contact with food, the MMC is replaced by contractions of variable amplitude and frequency, which enable mixing and digestion. The maximum contraction frequency is lower than during phase III of the MMC. The duration of these contractions is about 1 hour for each 200 kcal ingested. Segments of the small intestine that are not in contact with food maintain interdigestive motility.7Kellow J.E. Borody T.J. Phillips S.F. Tucker R.L. Haddad A.C. Human interdigestive motility variations in patterns from esophagus to colon.Gastroenterology. 1986; 91: 386-395Abstract PubMed Google Scholar Moreover, there are complex interactions of the different segments of the gastrointestinal tract that are in contact with food. The delivery of unabsorbed nutrients (including fats and complex carbohydrates) to the distal small intestine activates the ileal “brake,” whereby gastric and jejunal motility,8Spiller R.C. Trotman I.F. Higgins B.E. Ghatei M.A. Grimble G.K. Lee Y.C. Bloom S.R. Misiewicz J.J. Silk D.B. The ileal brake—inhibition of jejunal motility after ileal fat perfusion in man.Gut. 1984; 25: 365-374Crossref PubMed Google Scholar, 9Read N.W. McFarlane A. Kinsman R.I. Bates T.E. Blackhall N.W. Farrar G.B. Hall J.C. Moss G. Morris A.P. O’Neill B. et al.Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon.Gastroenterology. 1984; 86: 274-280PubMed Google Scholar gastric acid,10Clain J.E. Malagelada J.R. Go V.L. Summerskill W.H. Participation of the jejunum and ileum in postprandial gastric secretion in man.Gastroenterology. 1977; 73: 211-214PubMed Google Scholar and pancreatic secretion11Jain N.K. Boivin M. Zinsmeister A.R. DiMagno E.P. The ileum and carbohydrate-mediated feedback regulation of postprandial pancreaticobiliary secretion in normal humans.Pancreas. 1991; 6: 495-505Crossref PubMed Google Scholar are inhibited. These brake mechanisms are mediated through hormones and neural mechanisms.12Sarr M.G. Foley M.K. Winters R.C. Duenes J.A. DiMagno E.P. Role of extrinsic innervation in carbohydrate-induced ileal modulation of pancreatic secretion and upper gut function.Pancreas. 1997; 14: 166-173Crossref PubMed Google Scholar, 13Spiller R.C. Trotman I.F. Adrian T.E. Bloom S.R. Misiewicz J.J. Silk D.B. Further characterisation of the ’ileal brake’ reflex in man—effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.Gut. 1988; 29: 1042-1051Crossref PubMed Google Scholar, 14Van Citters G.W. Lin H.C. The ileal brake a fifteen-year progress report.Curr Gastroenterol Rep. 1999; 1: 404-409Crossref PubMed Google Scholar, 15Brown N.J. Rumsey R.D. Bogentoft C. Read N.W. The effect of an opiate receptor antagonist on the ileal brake mechanism in the rat.Pharmacology. 1993; 47: 230-236Crossref PubMed Google Scholar, 16Brown N.J. Horton A. Rumsey R.D. Read N.W. Granisetron and ondansetron effects on the ileal brake mechanism in the rat.J Pharm Pharmacol. 1993; 45: 521-524Crossref PubMed Google Scholar, 17Brown N.J. Rumsey R.D. Bogentoft C. Read N.W. The effect of adrenoceptor antagonists on the ileal brake mechanism in the rat.Br J Pharmacol. 1992; 105: 751-755Crossref PubMed Google Scholar When food is being ingested, a neurally mediated reflex relaxes the proximal stomach; arrival of food into the stomach enhances the process of accommodation (Figure 2A).4Thumshirn M. Camilleri M. Saslow S.B. Williams D.E. Burton D.D. Hanson R.B. Gastric accommodation in nonulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function.Gut. 1999; 44: 55-64Crossref PubMed Google Scholar, 5Kuiken S.D. Samsom M. Camilleri M. Mullan B.P. Burton D.D. Kost L.J. Hardyman T.J. O’Connor M.K. Development of a test to measure gastric accommodation in humans.Am J Physiol. 1999; 277: G1217-G1221PubMed Google Scholar, 6Bouras E.P. Delgado-Aros S. Camilleri M. Castillo E.J. Burton D.D. Thomforde G.M. Chial H.J. SPECT imaging of the stomach comparison with barostat and effects of sex, age, body mass index, and fundoplication.Gut. 2002; 51: 781-786Crossref PubMed Scopus (110) Google Scholar This allows ingestion of food without an increase in intragastric pressure or tension that would induce discomfort. Solid food is initially retained in the proximal stomach, while liquids tend to be distributed throughout the stomach. The proximal and distal stomach have different functions in dogs and humans.18Hinder R.A. Kelly K.A. Canine gastric emptying of solids and liquids.Am J Physiol. 1977; 233: E335-E340PubMed Google Scholar, 19Kelly K.A. Gastric emptying of liquids and solids roles of proximal and distal stomach.Am J Physiol. 1980; 239: G71-G76PubMed Google Scholar, 20Camilleri M. Malagelada J.-R. Brown M.L. Becker G. Zinsmeister A.R. Relation between antral motility and gastric emptying of solids and liquids in humans.Am J Physiol. 1985; 249: G580-G585PubMed Google Scholar, 21Azpiroz F. Malagelada J.-R. Gastric tone measured by an electronic barostat in health and postsurgical gastroparesis.Gastroenterology. 1987; 92: 934-943Abstract Full Text PDF PubMed Google Scholar, 22Houghton L.A. Read N.W. Heddle R. Horowitz M. Collins P.J. Chatterton B. Dent J. Relationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solid-liquid mixed meal.Gastroenterology. 1988; 94: 1285-1291Abstract PubMed Google Scholar Emptying of liquids from the stomach is faster than emptying of solids. The half-emptying time for nonnutrient liquids in healthy individuals is ∼20 minutes. Nonnutrient liquids empty from the stomach exponentially20Camilleri M. Malagelada J.-R. Brown M.L. Becker G. Zinsmeister A.R. Relation between antral motility and gastric emptying of solids and liquids in humans.Am J Physiol. 1985; 249: G580-G585PubMed Google Scholar, 23Elashoff J.D. Reedy T.J. Meyer J.H. Analysis of gastric emptying data.Gastroenterology. 1982; 83: 1306-1312PubMed Google Scholar; with increasing nutrient and calorie content of the liquid phase of the meal, there is a deceleration from an exponential to a more linear emptying.24Collins P.J. Houghton L.A. Read N.W. Horowitz M. Chatterton B.E. Heddle R. Dent J. Role of the proximal and distal stomach in mixed solid and liquid meal emptying.Gut. 1991; 32: 615-619Crossref PubMed Google Scholar Solids are retained selectively in the stomach while liquids start to empty; solids undergo “churning” or trituration by the high liquid shearing forces set up by circumferential contractions in the antrum as solids are propelled toward the closed pylorus. Acid and peptic digestion commences. Digestible food particles are emptied after their size has been reduced to ∼2 mm as a result of trituration.25MacGregor I.L. Martin P. Meyer J.H. Gastric emptying of solid food in normal man and after subtotal gastrectomy and truncal vagotomy with pyloroplasty.Gastroenterology. 1977; 72: 206-211Abstract Full Text PDF PubMed Google Scholar, 26Meyer J.H. Ohashi H. Jehn D. Thomson J.B. Size of liver particles emptied from the human stomach.Gastroenterology. 1981; 80: 1489-1496PubMed Google Scholar Thus, gastric emptying of solids is a 2-phase process: an initial lag or retention period, followed by a generally linear, postlag emptying phase.20Camilleri M. Malagelada J.-R. Brown M.L. Becker G. Zinsmeister A.R. Relation between antral motility and gastric emptying of solids and liquids in humans.Am J Physiol. 1985; 249: G580-G585PubMed Google Scholar, 27Siegel J.A. Urbain J.L. Adler L.P. Charkes N.D. Maurer A.H. Krevsky B. Knight L.C. Fisher R.S. Malmud L.S. Biphasic nature of gastric emptying.Gut. 1988; 29: 85-89Crossref PubMed Google Scholar The stomach empties solids completely over approximately 3–4 hours. However, the gastric emptying time is influenced by several factors discussed in the following text, including the volume, consistency, and fat content of the meal. In fact, the emptying of a very large, high-fat, solid meal may take even more than 4 hours. Several hormones modulate the motor and digestive process, including gastrin (eg, through acid secretion), CCK (eg, gallbladder contraction, bile and pancreatic secretion), and glucose-regulating hormones (eg, insulin, glucagon, incretins). Secretion of these hormones is integrated with the arrival of food or chyme in different levels of the gut to ensure delivery through the different regions of the gut at a rate to facilitate mixing and digestion. The volume response after a meal is demonstrable almost immediately after the meal and there is a gradual reduction in gastric volume such that, by 3 hours after meal ingestion, it is estimated that the calculated volume of meal in the stomach approximates the measured gastric volume (Figure 2B).28Burton D.D. Kim H.J. Camilleri M. Stephens D.A. Mullan B.P. O’Connor M.K. Talley N.J. Relationship of gastric emptying and volume changes after a solid meal in humans.Am J Physiol. 2005; 289: 261-266Google Scholar The nutrient content of a meal influences the rate of its emptying from the stomach. These principles are based on classic studies over two decades by Hunt et al.29Hunt J.N. Pathiak J.D. The osmotic effects of some simple molecules and ions on gastric emptying.J Physiol (Lond). 1960; 154: 254-269Google Scholar, 30Hunt J.N. Mechanisms and disorders of gastric emptying.Annu Rev Med. 1983; 34: 219-229Crossref PubMed Google Scholar Gastric emptying of liquid foods is so controlled that about 200 kcal/h is delivered to the duodenum. The volume of the meal and the meal proportions of carbohydrate and protein have minor effects on the rate of gastric emptying of calories. Hunt et al suggested that regulation of emptying is achieved through osmotic and calcium-binding properties of the products of digestion in the duodenum; calcium saponifies partially hydrolyzed triglycerides.29Hunt J.N. Pathiak J.D. The osmotic effects of some simple molecules and ions on gastric emptying.J Physiol (Lond). 1960; 154: 254-269Google Scholar, 30Hunt J.N. Mechanisms and disorders of gastric emptying.Annu Rev Med. 1983; 34: 219-229Crossref PubMed Google Scholar A CCK-mediated reflex is activated by chylomicrons or fatty acids with at least 12-carbon chains31Glatzle J. Wang Y. Adelson D.W. Kalogeris T.J. Zittel T.T. Tso P. Wei J.Y. Raybould H.E. Chylomicron components activate duodenal vagal afferents via a cholecystokinin A receptor-mediated pathway to inhibit gastric motor function in the rat.J Physiol. 2003; 550: 657-664Crossref PubMed Scopus (41) Google Scholar, 32Glatzle J. Kalogeris T.J. Zittel T.T. Guerrini S. Tso P. Raybould H.E. Chylomicron components mediate intestinal lipid-induced inhibition of gastric motor function.Am J Physiol. 2002; 282: G86-G91Google Scholar, 33Lal S. McLaughlin J. Barlow J. D’Amato M. Giacovelli G. Varro A. Dockray G.J. Thompson D.G. Cholecystokinin pathways modulate sensations induced by gastric distension in humans.Am J Physiol. 2004; 287: G72-G79Crossref PubMed Scopus (0) Google Scholar, 34Feinle C. D’Amato M. Read N.W. Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid.Gastroenterology. 1996; 110: 1379-1385Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar and inhibits antral motility35Heddle R. Dent J. Read N.W. Houghton L.A. Toouli J. Horowitz M. Maddern G.J. Downton J. Antropyloroduodenal motor responses to intraduodenal lipid infusion in healthy volunteers.Am J Physiol. 1988; 254: G671-G679PubMed Google Scholar; although chylomicrons activate CCK release in rats,31Glatzle J. Wang Y. Adelson D.W. Kalogeris T.J. Zittel T.T. Tso P. Wei J.Y. Raybould H.E. Chylomicron components activate duodenal vagal afferents via a cholecystokinin A receptor-mediated pathway to inhibit gastric motor function in the rat.J Physiol. 2003; 550: 657-664Crossref PubMed Scopus (41) Google Scholar this has not yet been shown in humans. Fat in the duodenum, such as oleic acid, delays gastric emptying,36Keinke O. Ehrlein H.J. Effect of oleic acid on canine gastroduodenal motility, pyloric diameter and gastric emptying.Q J Exp Physiol. 1983; 68: 675-686PubMed Google Scholar, 37Lin H.C. van Citters G.W. Heimer F. Bonorris G. Slowing of gastrointestinal transit by oleic acid a preliminary report of a novel, nutrient-based treatment in humans.Dig Dis Sci. 2001; 46: 223-229Crossref PubMed Scopus (17) Google Scholar but there is some adaptation of gastric function to the effects of diet. Thus, a high-fat diet may not alter the gastric emptying rate of carbohydrate test meals, and adaptation after a high-fat diet led to acceleration, rather than slowing, of the (postlag) emptying of a high-fat test meal.38Castiglione K.E. Read N.W. French S.J. Adaptation to high-fat diet accelerates emptying of fat but not carbohydrate test meals in humans.Am J Physiol. 2002; 282: R366-R371Crossref Google Scholar Similarly, in rats, feeding a high-fat diet diminishes the enterogastric inhibition of gastric emptying by intestinal oleate and diminishes the ability of CCK to inhibit gastric emptying.39Covasa M. Ritter R.C. Adaptation to high-fat diet reduces inhibition of gastric emptying by CCK and intestinal oleate.Am J Physiol. 2000; 278: R166-R170Google Scholar The small intestine transports solids and liquids at approximately the same rate; the head of the column of liquid chyme may reach the cecum as early as 30 minutes after ingestion. As a result of the lag phase for the transport of solids from the stomach, liquids typically arrive in the colon before solids. However, it takes about 150 minutes for half the solid and liquid chyme of similar caloric density (assuming solids are presented in a triturated form to the small bowel) to traverse the small bowel.40Camilleri M. Brown M.L. Malagelada J.R. Impaired transit of chyme in chronic intestinal pseudoobstruction. Correction by cisapride.Gastroenterology. 1986; 91: 619-626Abstract PubMed Google Scholar This was demonstrated by comparison of overall duodenocecal transit times in healthy subjects using scintigraphy40Camilleri M. Brown M.L. Malagelada J.R. Impaired transit of chyme in chronic intestinal pseudoobstruction. Correction by cisapride.Gastroenterology. 1986; 91: 619-626Abstract PubMed Google Scholar and by Kerlin et al, who infused different-consistency nutrients into the distal small intestine and observed similar flow rates for “solids” and liquids using an intubated method.41Kerlin P. Zinsmeister A. Phillips S.F. Relationship of motility to flow of contents in the human small intestine.Gastroenterology. 1982; 82: 701-706PubMed Google Scholar Chyme moves from ileum to colon intermittently in boluses, and the bolus movement is believed to result from a specialized contractile process, the prolonged propagated contraction.5Kuiken S.D. Samsom M. Camilleri M. Mullan B.P. Burton D.D. Kost L.J. Hardyman T.J. O’Connor M.K. Development of a test to measure gastric accommodation in humans.Am J Physiol. 1999; 277: G1217-G1221PubMed Google Scholar, 42Greydanus M.P. Camilleri M. Colemont L.J. Phillips S.F. Brown M.L. Thomforde G.M. Ileocolonic transfer of solid chyme in small intestinal neuropathies and myopathies.Gastroenterology. 1990; 99: 158-164Abstract PubMed Google Scholar, 43Kerlin P. Phillips S. Differential transit of liquids and solid residue through the human ileum.Am J Physiol. 1983; 245: G38-G43PubMed Google Scholar, 44Quigley E.M. Borody T.J. Phillips S.F. Wienbeck M. Tucker R.L. Haddad A. Motility of the terminal ileum and ileocecal sphincter in healthy humans.Gastroenterology. 1984; 87: 857-866PubMed Google Scholar There is evidence of feedback control of proximal small intestinal motility by complex carbohydrates or fat that reach the distal small intestine. Pharmacologic studies suggest that opiate, serotonergic, and adrenergic mechanisms are involved in feedback regulation.14Van Citters G.W. Lin H.C. The ileal brake a fifteen-year progress report.Curr Gastroenterol Rep. 1999; 1: 404-409Crossref PubMed Google Scholar, 45Lin H.C. Zhao X.T. Wang L. Intestinal transit is more potently inhibited by fat in the distal (ileal brake) than in the proximal (jejunal brake) gut.Dig Dis Sci. 1997; 42: 19-25Crossref PubMed Scopus (45) Google Scholar, 46Lin H.C. Zhao X.T. Wang L. Fat absorption is not complete by midgut but is dependent on load of fat.Am J Physiol. 1996; 271: G62-G67PubMed Google Scholar, 47Lin H.C. Zhao X.T. Wang L. Wong H. Fat-induced ileal brake in the dog depends on peptide YY.Gastroenterology. 1996; 110: 1491-1495Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 48Lin H.C. Zhao X.T. Wang L. Jejunal brake inhibition of intestinal transit by fat in the proximal small intestine.Dig Dis Sci. 1996; 41: 326-329Crossref PubMed Google Scholar Gastric acid secretion is also regulated by the central nervous system, the enteric nervous system, and a complex network of neuroendocrine cells acting in an autocrine or paracrine manner.49Schmidt W.E. Bojko J.B. Regulation of gastric acid secretion.in: Greeley G.H. Gastrointestinal endocrinology. Humana, Totowa, NJ1998: 353-391Google Scholar, 50Schubert M.L. Gastric secretion.Curr Opin Gastroenterol. 2003; 19: 519-525Crossref PubMed Scopus (24) Google Scholar These converge on the G cells (source of gastrin) in the antrum and the parietal cells of the fundic and body mucosa, which are the source of hydrochloric acid. Knockout models have provided significant insights on the control of acid secretion.51Schmidt W.E. Schmitz F. Genetic dissection of the secretory machinery in the stomach.Gastroenterology. 2004; 126: 606-609Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Gastrin is responsible for at least 50% of the postprandial acid release.52Kovacs T.O. Walsh J.H. Maxwell V. Wong H.C. Azuma T. Katt E. Gastrin is a major mediator of the gastric phase of acid secretion in dogs proof by monoclonal antibody neutralization.Gastroenterology. 1989; 97: 1406-1413PubMed Google Scholar Gastrin also stimulates mucosal growth in the stomach that results in hyperplasia of the enterochromaffin-like (ECL) and parietal cells.53Crean G.P. Marshall M.W. Rumsey R.D. Parietal cell hyperplasia induced by the administration of pentagastrin (ICI 50,123) to rats.Gastroenterology. 1969; 57: 147-155Abstract Full Text PDF PubMed Google Scholar Gastrin stimulation of acid secretion in response to a meal is mediated through direct activation of CCK2 receptors on parietal cells and through release of histamine from ECL cells (Figure 3). The structural relationship of CCK to gastrin and the high affinity of the 2 peptides for CCK2 receptors suggest that CCK may peripherally modulate gastric acid secretion (Figure 3). However, the literature provides conflicting evidence.54Grossman M.I. Regulation of gastric acid secretion.in: Johnson L.R. Physiology of the gastrointestinal tract. Raven, New York1984: 659-672Google Scholar, 55Wank S.A. G protein-coupled receptors in gastrointestinal physiology. I. CCK receptors an exemplary family.Am J Physiol. 1998; 274: G607-G613PubMed Google Scholar In CCK2 receptor–null (gene knockout) mice, there is markedly impaired gastric acid secretion, atrophy of the oxyntic mucosa, and hypergastrinemia.56Chen D. Zhao C.M. Hakanson R. Rehfeld J.F. Gastric phenotypic abnormality in cholecystokinin 2 receptor null mice.Pharmacol Toxicol. 2002; 91: 375-381Crossref PubMed Scopus (8) Google Scholar Simultaneous infusion of CCK and the selective CCK1 receptor antagonist loxiglumide converted CCK into a powerful acid secretagogue and resulted in a near-maximal acid response. On the other hand, the overall effect of CCK may be to down-regulate stimulated acid secretion; CCK induces release of somatostatin, which in turn tonically inhibits parietal cells, ECL cells, and gastrin-producing G cells; infusion of in vivo CCK acts as a negative regulator of gastric acid secretion and postprandial release of gastrin57Schmidt W.E. Schenk S. Nustede R. Holst J.J. Folsch U.R. Creutzfeldt W. Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans.Gastroenterology. 1994; 107: 1610-1620PubMed Google Scholar; and targeted disruption of the CCK gene restores impaired acid secretion caused by functional inactivation of the gastrin gene.58Chen D. Zhao C.M. Hakanson R. Samuelson L.C. Rehfeld J.F. Friis-Hansen L. Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice.Gastroenterology. 2004; 126: 476-487Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Gastric acid may affect the efficiency and kinetics of the digestion and absorption of nutrients either directly (eg, by an alteration of digestive enzyme activity) or indirectly (eg, by the prevention of bacterial overgrowth). Gastric acid secretion protects the upper gastrointestinal tract from bacterial colonization; below pH 4, many bacteria do not survive longer than 10 minutes,59Theisen J. Nehra D. Citron D. Johansson J. Hagen J.A. Crookes P.F. DeMeester S.R. Bremner C.G. DeMeester T.R. Peters J.H. Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids.J Gastrointest Surg. 2000; 4: 50-54Crossref PubMed Google Scholar although some (eg, Listeria species60Ferreira A. Sue D. O’Byrne C.P. Boor K.J. Role of Listeria monocytogenes sigma(B) in survival of lethal acidic conditions and in the acquired acid tolerance response.Appl Environ Microbiol. 2003; 69: 2692-2698Crossref PubMed Scopus (85) Google Scholar) have developed defense mechanisms that enable survival below pH 4. The digestion and absorption of macronutrients, minerals, and vitamins are dependent on intraluminal pH at several steps in the process. Intragastric pH in healthy subjects is in the 2.0–2.5 range before meals and in the 4.5–5.8 range during and immediately af" @default.
• W2078604556 created "2016-06-24" @default.
• W2078604556 creator A5017598516 @default.
• W2078604556 date "2006-08-01" @default.
• W2078604556 modified "2023-09-24" @default.
• W2078604556 title "Integrated Upper Gastrointestinal Response to Food Intake" @default.
• W2078604556 cites W1486241417 @default.
• W2078604556 cites W1502152603 @default.
• W2078604556 cites W151161960 @default.
• W2078604556 cites W1517722308 @default.
• W2078604556 cites W1532838319 @default.
• W2078604556 cites W1542535615 @default.
• W2078604556 cites W1577116501 @default.
• W2078604556 cites W1583115094 @default.
• W2078604556 cites W1608840883 @default.
• W2078604556 cites W1618681344 @default.
• W2078604556 cites W1637971961 @default.
• W2078604556 cites W1640733839 @default.
• W2078604556 cites W1646455039 @default.
• W2078604556 cites W1660572521 @default.
• W2078604556 cites W1731897847 @default.
• W2078604556 cites W1775278867 @default.
• W2078604556 cites W1781900710 @default.
• W2078604556 cites W1798533447 @default.
• W2078604556 cites W180897439 @default.
• W2078604556 cites W1826075907 @default.
• W2078604556 cites W1841462180 @default.
• W2078604556 cites W1905174418 @default.
• W2078604556 cites W1941449984 @default.
• W2078604556 cites W1960059531 @default.
• W2078604556 cites W1965138514 @default.
• W2078604556 cites W1967102597 @default.
• W2078604556 cites W1967233987 @default.
• W2078604556 cites W1968716069 @default.
• W2078604556 cites W1975756049 @default.
• W2078604556 cites W1975763485 @default.
• W2078604556 cites W1983928000 @default.
• W2078604556 cites W1984345984 @default.
• W2078604556 cites W1985901674 @default.
• W2078604556 cites W1987187364 @default.
• W2078604556 cites W1987493915 @default.
• W2078604556 cites W1989343508 @default.
• W2078604556 cites W1990095603 @default.
• W2078604556 cites W1996559176 @default.
• W2078604556 cites W1996713062 @default.
• W2078604556 cites W1999598420 @default.
• W2078604556 cites W1999883198 @default.
• W2078604556 cites W2002549791 @default.
• W2078604556 cites W2003500623 @default.
• W2078604556 cites W2005894604 @default.
• W2078604556 cites W2007701360 @default.
• W2078604556 cites W2012853846 @default.
• W2078604556 cites W2013395086 @default.
• W2078604556 cites W2013989224 @default.
• W2078604556 cites W2014486960 @default.
• W2078604556 cites W2022018558 @default.
• W2078604556 cites W2024577438 @default.
• W2078604556 cites W2028272916 @default.
• W2078604556 cites W2028308157 @default.
• W2078604556 cites W2028921955 @default.
• W2078604556 cites W2030081534 @default.
• W2078604556 cites W2032006080 @default.
• W2078604556 cites W2037328290 @default.
• W2078604556 cites W2039339837 @default.
• W2078604556 cites W2042160000 @default.
• W2078604556 cites W2045078355 @default.
• W2078604556 cites W2045948521 @default.
• W2078604556 cites W2046036438 @default.
• W2078604556 cites W2047421149 @default.
• W2078604556 cites W2049158743 @default.
• W2078604556 cites W2050112177 @default.
• W2078604556 cites W2050931629 @default.
• W2078604556 cites W2051753034 @default.
• W2078604556 cites W2051780334 @default.
• W2078604556 cites W2053916731 @default.
• W2078604556 cites W2058039522 @default.
• W2078604556 cites W2059340303 @default.
• W2078604556 cites W2059535503 @default.
• W2078604556 cites W2059635041 @default.
• W2078604556 cites W2060599734 @default.
• W2078604556 cites W2060745099 @default.
• W2078604556 cites W2060927585 @default.
• W2078604556 cites W2061274996 @default.
• W2078604556 cites W2066486037 @default.
• W2078604556 cites W2066965048 @default.
• W2078604556 cites W2067891814 @default.
• W2078604556 cites W2069006090 @default.
• W2078604556 cites W2069835983 @default.
• W2078604556 cites W2072370191 @default.
• W2078604556 cites W2074613129 @default.
• W2078604556 cites W2078268286 @default.
• W2078604556 cites W2079746667 @default.
• W2078604556 cites W2081129782 @default.
• W2078604556 cites W2081666098 @default.
• W2078604556 cites W2083099752 @default.
• W2078604556 cites W2083142774 @default.
• W2078604556 cites W2084080125 @default.
• W2078604556 cites W2085957056 @default.

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