Abstract
There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II,N=6), and during endogenous stimulation by intraduodenal essential amino acid perfusion,N=6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P<0.01), and endogenously stimulated output by 68%, respectively (P<0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80–100% (allP<0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein, Decreased acid output is associated with release of GLP-1, but not PYY. These findings support the hypothesis that the distal small intestine may participate in the late postprandial inhibitory regulation of gastric secretory function in humans and that GLP-1 may be an intermediary factor.
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Fone RD, Horowitz M, Read NW, Dent J, Maddox A: The effect of terminal ileal triglyceride infusion on gastroduodenal motility and the intragastric distribution of a solid meal. Gastroenterology 98:568–575, 1990
Jain NK, Boivin M, Zinsmeister AR, Brown M, Malagelada JR, DiMagno EP: Effect of perfusing carbohydrates and amylase inhibitor into the ileum on gastrointestinal hormones and gastric emptying of homogenized meal. Gastroenterology 96:377–387, 1989
Layer P, Zinsmeister AR, DiMagno EP: Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans. Gastroenterology 91:41–48, 1986
Read NW, McFarlane A, Kinsman RJ, Bates TE, Blackhall NW, Farrar GBJ, Hall JC, Moss G, Morris AP, O'Neill B, Welch I, Lee Y, Bloom SR: Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon. Gastroenterology 86:274–280, 1984
Spiller RC, Trotman IF, Adrian TE, Bloom SR, Misiewicz JJ, Silk DBA: 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 29:1042–1051, 1988
Spiller RC, Trotman IF, Higgins BE, Ghatei MA, Grimble K, Lee YC, Bloom SR, Misiewicz JJ, Silk DBA: The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut 25:365–374, 1984
Layer P, Peschel S, Schlesinger T, Goebell H: Human pancreatic secretion and intestinal motility: Effects of ileal nutrient perfusion. Am J Physiol 258(Gastrointest Liver Physiol 21):G196-G201, 1990
Owyang C, Green L, Rader D: Colonic inhibition of pancreatic and biliary secretion. Gastroenterology 84:470–475, 1983
Clain JE, Go VLW, Malagelada JR: Inhibitory role of the distal small intestine on the gastric secretory response to meals in man. Gastroenterology 74:704–707, 1978
Jian R, Besterman HS, Sarson DL, et al: Colonic inhibition of gastric secretion in man. Dig Dis Sci 26:195–201, 1981
Seal AM, Debas HT: Colonic inhibition of gastric aicd secretion in the dog. Gastroenterology 79:823–826, 1980
Soon-Shiong P, Debas HT, Seal AM, et al: Colonic inhibition of gastric acid secretion in man. Surg Forum 31:152–154, 1980
Anderson IH, Levine AS, Levitt MD: Incomplete absorption of the carbohydrate in all-purpose wheat flour. N Engl J Med 304:891–892, 1981
Levitt MD, Hirsh P, Fetzer CA, Sheahan M, Levine AS: H2 excretion after ingestion of complex carbohydrates. Gastroenterology 92:383–389, 1987
Stephen AM, Haddad AC, Phillips SF: Passage of carbohydrate into the colon. Gastroenterology 85:589–595, 1983
Adrian T, Savage A, Sagor G, Allen J, Bacarese-Hamilton A, Tatemoto K, Polak J, Bloom S: Effect of peptide YY on gastric, pancreatic, and biliary function in humans. Gastroenterology 89:494–499, 1985
Kreyman B, Ghatei MA, Williams G, Bloom SR: Glucagon-like peptide-1 (7–36): A physiological incretin in man. Lancet 2:1300–1304, 1987
Schjoldager BTG, Mortensen PE, Christiansen J, Ørskov C, Holst JJ: GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. Dig Dis Sci 34:703–708, 1989
Gutniak M, Ørskov C, Holst JJ, Ahrén B, Efendic S: Antidiabetogenic effect of glucagon-like peptide-1 (7–36) amide in normal subjects and patient with diabetes mellitus. N Engl J Med 326:1316–1322, 1992
O'Halloran DJ, Nikou GC, Kreyman B, Ghatei MA, Bloom SR: Glucagon-like peptide-1 (7–36)-NH2: A physiological inhibitor of the gastric acid secretion in man. J Endocrinol 126:169–173, 1990
Go VLW, Hofmann AF, and Summerskill WHJ: Simultaneous measurements of total pancreatic, biliary and gastric outputs in man using a perfusion technique. Gastroenterology 58:321–328, 1970
Layer P, Chan ATH, Go VLW, DiMagno EP: Human pancreatic secretion during phase II antral motility of the interdigestive cycle. Am J Physiol 254(Gastrointest Liver Physiol 17):G249–G253, 1988
Layer P, Go VLW, DiMagno EP: Fate of pancreatic enzymes during aboral small intestinal transit in humans. Am J Physiol 251(Gastrointest Liver Physiol 14):G475-G480, 1986
Layer P, Jansen JBMJ, Cherian L, Lamers CBHW, Goebell H: Feedback regulation of human pancreatic secretion: Effects of protease inhibition on duodenal delivery and small intestinal transit of pancreatic enzymes. Gastroenterology 98:1311–1319, 1990
Holst JJ, Bersani M: Assays for peptide products of somatostatin gene expression. In Methods in Neurosciences, Vol 5: Neuropeptide Technology. P. Michael Conn (Ed). San Diego, Academic Press, 1991, pp 3–22
Ekman R, Wahlestedt C, Böttcher G, Sundler F, Hakanson R, Panula P: Peptide YY-like immunoreactivity in the central nervous system of the rat. Regul Pept 16:157–168, 1986
Ørskov C, Jeppesen J, Madsbad S, Holst JJ: Proglucagon products in plasma of noninsulin-dependent diabetics and non-diabetic controls in the fasting state and after oral glucose and intravenous arginine. J Clin Invest 87:415–423, 1991
Box GEP, Hunter WS, Hunter JS: Statistics for Experimenters. New York, John Wiley & Sons, 1978
MIller LJ, Malagelada J-R, Taylor WF, Go VLW: Intestinal control of human postprandial gastric function: The role of components of jejunoileal chyme in regulating gastric secretion and gastric emptying. Gastroenterology 80:763–769, 1981
Hesselfeldt P, Christiansen J, Rehfeld JF, Backer O: Meal stimulated gastric acid and gastrin secretion before and after jejuno-ileal shunt operation in obese patients. Scand J Gastroenterol 14:13–16, 1979
Konturek SJ, Radecki T, Kwiecien N. Stimuli for intestinal phase of gastric secretion in dogs. Am J Physiol 234:E64-E69, 1978
Azpiroz F, Malagelada J-R: Intestinal control of gastric tone. Am J Physiol 249:G501-G509, 1985
Jain NK, Boivin M, Zinsmeister AR, DiMagno EP: The ileum and carbohydrate-mediated feedback regulation of postprandial pancreaticobiliary secretion in normal humans. Pancreas 6:495–505, 1991
Layer P, Schlesinger T, Gröger G, Goebell H: Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum. Pancreas 8:426–432, 1993
Adrian TE, Ferri GL, Bacarese-Hamilton AJ, et al: Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89:1070–1077, 1985
Savage AP, Gornacz GE, Adrian TE, Ghatei MA, Goodlad RA, Wright NA, Bloom SR: Is raised plasma peptide YY after intestinal resection in the rat responsible for the trophic response? Gut 26:1353–1358, 1985
Adrian TE, Savage AP, Bacarese-Hamilton AJ: Peptide YY abnormalities in gastrointestinal diseases. Gastroenterology 90:379–384, 1986
Andrews NJ, Irving MH: Human gut hormone profiles in patients with short bowel syndrome. Dig Dis Sci 37:729–732, 1992
Greeley GH Jr, Hashimoto T, Izukura M, Gomez G, Jeng J, Hill FLC, Lluis F, Thompson JC: A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide YY in the dog. Endocrinology 125:1761–1765, 1989
Greeley GH Jr, Jeng YJ, Gomez G, Hashimoto T, Hill FLC, Kern K, Kurosky T, Chuo HF, Thompson JC: Evidence for regulation of peptide-YY release by the proximal gut. Endocrinology 124:1438–1443, 1989
Olsen PS, Pedersen JH, Kirkegaard P, Been H, Stadil F, Fahrenkrug J, Christiansen J: Neurotensin induced inhibition of acid secretion in duodenal ulcer patients before and after vagotomy. Gut 25:481–484, 1984
Mogard MH, Maxwell VE, Sytnik B, Walsh JH: Regulation of gastric acid secretion by neurotensin in man: Evidence against a hormonal role. J Clin Invest 80:1064–1067, 1987
Kirkegaard P, Loud FB, Moody AJ, Holst JJ, Christiansen J: Gut GLI inhibits gastric acid secretion in the rat. Nature 297:156–157, 1982
Schjoldager BTG, Mortensen PE, Myhren J, Christiansen J, Holst JJ: Oxyntomodulin from distal gut: Role in regulation of gastric and pancreatic function. Dig Dis Sci 34:1411–1419, 1989
Holst JJ, Ørskov C, Nielsen OV, Schwartz TW: Truncated GLP-1, an insulin-releasing hormone from distal gut. FEBS Lett 211:169–174, 1987
Ørskov C, Bersani M, Johnsen AH, Højrup P, Holst JJ: Complete sequence of glucagon-like peptide-1 (GLP-1) from human and pig small intestine. J Biol Chem 264:12826–12829, 1989
Wettergren A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ: Truncated glucagon-like peptide-1 (proglucagon 78–107 amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci (in press).
Schmidtler J, Schepp W, Janczewska I, Weigert N, Fürlinger C, Schusdziarra V, Classen M: GLP-1 (7–37), and -(1–36) amide: Potent cAMP-dependent stimuli of rat parietal cell function. Am J Physiol 260(Gastrointest Liver Physiol 23):G940-G950, 1991
Orskov C, Holst JJ, Nielsen OV: Effect of truncated glucagon-like peptide-1 (proglucagon-(78–107) amide) on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinology 123:2009–2013, 1988
Eissele R, Koop H, Arnold R: Effect of glucagon-like peptide 1 on gastric somatostatin and gastrin secretion in the rat. Scand J Gastroenterol 25:449–454, 1990
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This work was supported by Deutsche Forschungsgemeinschaft, grant La 483/5-2, and Danish Medical Research Council.
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Layer, P., Juul Holst, J., Grandt, D. et al. Ileal release of glucagon-like peptide-1 (GLP-1). Digest Dis Sci 40, 1074–1082 (1995). https://doi.org/10.1007/BF02064202
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DOI: https://doi.org/10.1007/BF02064202