Enterohormones and the Response to Critical Illness

  • Mark P. PlummerEmail author
  • Annika Reintam Blaser
  • Adam M. Deane


The secretion of a number of enterohormones is disordered in the critically ill which may mediate abnormalities in motility and glycaemia. However, these mediators can also potentially serve a protective role, dampening inflammation and modulating the enteral immune response. There are over 30 recognised enterohormones, and therapeutic manipulation of specific enterohormones or their receptors is a burgeoning area of critical care research with promising preclinical data and an increasing number of small clinical trials. Further characterisation of the effect of critical illness on the endocrine gut and how it can be manipulated to improve outcomes in critical illness warrants evaluation.


Gastric Emptying Critical Illness Delayed Gastric Emptying Gastric Inhibitory Polypeptide Stress Hyperglycaemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Rehfeld JF (2012) Beginnings: a reflection on the history of gastrointestinal endocrinology. Regul Pept 177(Suppl):S1–S5CrossRefPubMedGoogle Scholar
  2. 2.
    Schmidt WE (1997) The intestine, an endocrine organ. Digestion 58(Suppl 1):56–58CrossRefPubMedGoogle Scholar
  3. 3.
    Thompson JS (1995) The intestinal response to critical illness. Am J Gastroenterol 90(2):190–200PubMedGoogle Scholar
  4. 4.
    Deane A, Chapman MJ, Fraser RJ, Horowitz M (2010) Bench-to-bedside review: the gut as an endocrine organ in the critically ill. Crit Care 14(5):228CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Parker BA, Doran S, Wishart J, Horowitz M, Chapman IM (2005) Effects of small intestinal and gastric glucose administration on the suppression of plasma ghrelin concentrations in healthy older men and women. Clin Endocrinol 62(5):539–546CrossRefGoogle Scholar
  6. 6.
    Crona D, MacLaren R (2012) Gastrointestinal hormone concentrations associated with gastric feeding in critically ill patients. JPEN J Parenter Enteral Nutr 36(2):189–196CrossRefPubMedGoogle Scholar
  7. 7.
    Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762):656–660CrossRefPubMedGoogle Scholar
  8. 8.
    Muller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F et al (2015) Ghrelin. Mol Metab 4(6):437–460CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Tack J, Depoortere I, Bisschops R, Delporte C, Coulie B, Meulemans A, Janssens J, Peeters T (2006) Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut 55(3):327–333CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    De Winter BY, De Man JG, Seerden TC, Depoortere I, Herman AG, Peeters TL, Pelckmans PA (2004) Effect of ghrelin and growth hormone-releasing peptide 6 on septic ileus in mice. J Neurogastroenterol Motil 16(4):439–446CrossRefGoogle Scholar
  11. 11.
    Ejskjaer N, Vestergaard ET, Hellstrom PM, Gormsen LC, Madsbad S, Madsen JL, Jensen TA, Pezzullo JC, Christiansen JS, Shaughnessy L et al (2009) Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Aliment Pharmacol Ther 29(11):1179–1187CrossRefPubMedGoogle Scholar
  12. 12.
    Koch A, Sanson E, Helm A, Voigt S, Trautwein C, Tacke F (2010) Regulation and prognostic relevance of serum ghrelin concentrations in critical illness and sepsis. Crit Care 14(3):R94CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cummings DE, Overduin J (2004) Circulating Ghrelin levels in pathophysiological conditions. In: Ghigo E (ed) Ghrelin. Springer Science + Business Media, Boston, pp 213–214Google Scholar
  14. 14.
    Wu R, Dong W, Cui X, Zhou M, Simms HH, Ravikumar TS, Wang P (2007) Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve. Ann Surg 245(3):480–486CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wang W, Bansal S, Falk S, Ljubanovic D, Schrier R (2009) Ghrelin protects mice against endotoxemia-induced acute kidney injury. Am J Physiol Renal Physiol 297(4):F1032–F1037CrossRefPubMedGoogle Scholar
  16. 16.
    Wu R, Dong W, Qiang X, Wang H, Blau SA, Ravikumar TS, Wang P (2009) Orexigenic hormone ghrelin ameliorates gut barrier dysfunction in sepsis in rats. Crit Care Med 37(8):2421–2426CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wu R, Dong W, Zhou M, Zhang F, Marini CP, Ravikumar TS, Wang P (2007) Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats. Am J Respir Crit Care Med 176(8):805–813CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wu R, Dong W, Zhou M, Cui X, Hank Simms H, Wang P (2005) Ghrelin improves tissue perfusion in severe sepsis via downregulation of endothelin-1. Cardiovasc Res 68(2):318–326CrossRefPubMedGoogle Scholar
  19. 19.
    Garin MC, Burns CM, Kaul S, Cappola AR (2013) Clinical review: the human experience with ghrelin administration. J Clin Endocrinol Metab 98(5):1826–1837CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Doig GS, Simpson F, Finfer S, Delaney A, Davies AR, Mitchell I, Dobb G (2008) Nutrition Guidelines Investigators of the ACTG: effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. JAMA 300(23):2731–2741CrossRefPubMedGoogle Scholar
  21. 21.
    Poitras P, Peeters TL (2008) Motilin. Curr Opin Endocrinol Diabetes Obes 15(1):54–57CrossRefPubMedGoogle Scholar
  22. 22.
    Vantrappen G, Janssens J, Peeters TL, Bloom SR, Christofides ND, Hellemans J (1979) Motilin and the interdigestive migrating motor complex in man. Dig Dis Sci 24(7):497–500CrossRefPubMedGoogle Scholar
  23. 23.
    Peeters TL, Muls E, Janssens J, Urbain JL, Bex M, Van Cutsem E, Depoortere I, De Roo M, Vantrappen G, Bouillon R (1992) Effect of motilin on gastric emptying in patients with diabetic gastroparesis. Gastroenterology 102(1):97–101PubMedGoogle Scholar
  24. 24.
    Janssens J, Peeters TL, Vantrappen G, Tack J, Urbain JL, De Roo M, Muls E, Bouillon R (1990) Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. N Engl J Med 322(15):1028–1031CrossRefPubMedGoogle Scholar
  25. 25.
    Nguyen NQ, Chapman MJ, Fraser RJ, Bryant LK, Holloway RH (2007) Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness. Crit Care Med 35(2):483–489CrossRefPubMedGoogle Scholar
  26. 26.
    MacLaren R, Kiser TH, Fish DN, Wischmeyer PE (2008) Erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric nutrition in critically ill patients. JPEN J Parenter Enteral Nutr 32(4):412–419CrossRefPubMedGoogle Scholar
  27. 27.
    Dive A, Miesse C, Galanti L, Jamart J, Evrard P, Gonzalez M, Installe E (1995) Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients: a double-blind, randomized, placebo-controlled study. Crit Care Med 23(8):1356–1362CrossRefPubMedGoogle Scholar
  28. 28.
    Gungabissoon U, Hacquoil K, Bains C, Irizarry M, Dukes G, Williamson R, Deane AM, Heyland DK (2015) Prevalence, risk factors, clinical consequences, and treatment of enteral feed intolerance during critical illness. JPEN J Parenter Enteral Nutr 39(4):441–448CrossRefPubMedGoogle Scholar
  29. 29.
    Sanger GJ, Wang Y, Hobson A, Broad J (2013) Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists. Br J Pharmacol 170(7):1323–1332CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Chapman MJ, Fraser R, Nguyen NQ, Deane AM, O'Conner SN, Duncan R, Hacquoil K, Vasist L, Barton M, Dukes G (2011) The effect of GSK962040, a selective motilin agonist, on gastric emptying in critically ill patients with enteral feed intolerance (Mot112572). Crit Care Med 39(12):195Google Scholar
  31. 31.
    Pilichiewicz AN, Chaikomin R, Brennan IM, Wishart JM, Rayner CK, Jones KL, Smout AJ, Horowitz M, Feinle-Bisset C (2007) Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men. Am J Physiol Endocrinol Metab 293(3):E743–E753CrossRefPubMedGoogle Scholar
  32. 32.
    Luttikhold J, de Ruijter FM, van Norren K, Diamant M, Witkamp RF, van Leeuwen PA, Vermeulen MA (2013) Review article: the role of gastrointestinal hormones in the treatment of delayed gastric emptying in critically ill patients. Aliment Pharmacol Ther 38(6):573–583CrossRefPubMedGoogle Scholar
  33. 33.
    Wank SA (1995) Cholecystokinin receptors. Am J Physiol 269(5 Pt 1):G628–G646PubMedGoogle Scholar
  34. 34.
    Fried M, Erlacher U, Schwizer W, Lochner C, Koerfer J, Beglinger C, Jansen JB, Lamers CB, Harder F, Bischof-Delaloye A et al (1991) Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin-receptor antagonist loxiglumide. Gastroenterology 101(2):503–511PubMedGoogle Scholar
  35. 35.
    Rayner CK, Park HS, Doran SM, Chapman IM, Horowitz M (2000) Effects of cholecystokinin on appetite and pyloric motility during physiological hyperglycemia. Am J Physiol Gastrointest Liver Physiol 278(1):G98–G104PubMedGoogle Scholar
  36. 36.
    Nguyen NQ, Fraser RJ, Chapman MJ, Bryant LK, Holloway RH, Vozzo R, Wishart J, Feinle-Bisset C, Horowitz M (2007) Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations. Crit Care Med 35(1):82–88CrossRefPubMedGoogle Scholar
  37. 37.
    Nguyen NQ, Fraser RJ, Chapman M, Bryant LK, Wishart J, Holloway RH, Horowitz M (2006) Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness and associated with feed intolerance: an observational, controlled study. Crit Care 10(6):R175CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Deane AM, Nguyen NQ, Stevens JE, Fraser RJ, Holloway RH, Besanko LK, Burgstad C, Jones KL, Chapman MJ, Rayner CK et al (2010) Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia. J Clin Endocrinol Metab 95(1):215–221CrossRefPubMedGoogle Scholar
  39. 39.
    Plummer MP, Jones KL, Annink CE, Cousins CE, Meier JJ, Chapman MJ, Horowitz M, Deane AM (2014) Glucagon-like peptide 1 attenuates the acceleration of gastric emptying induced by hypoglycemia in healthy subjects. Diabetes Care 37(6):1509–1515CrossRefPubMedGoogle Scholar
  40. 40.
    Luyer MD, Greve JW, Hadfoune M, Jacobs JA, Dejong CH, Buurman WA (2005) Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med 202(8):1023–1029CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    de Haan JJ, Lubbers T, Hadfoune M, Luyer MD, Dejong CH, Buurman WA, Greve JW (2008) Postshock intervention with high-lipid enteral nutrition reduces inflammation and tissue damage. Ann Surg 248(5):842–848CrossRefPubMedGoogle Scholar
  42. 42.
    Schirra J, Katschinski M, Weidmann C, Schafer T, Wank U, Arnold R, Goke B (1996) Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest 97(1):92–103CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Plummer MP, Chapman MJ, Horowitz M, Deane AM (2014) Incretins and the intensivist: what are they and what does an intensivist need to know about them? Crit Care 18(1):205CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Campbell JE, Drucker DJ (2013) Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab 17(6):819–837CrossRefPubMedGoogle Scholar
  45. 45.
    Nauck M, Stockmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29(1):46–52CrossRefPubMedGoogle Scholar
  46. 46.
    Perley MJ, Kipnis DM (1967) Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 46(12):1954–1962CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, Goke B (2006) Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut 55(2):243–251CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Edwards CM, Todd JF, Mahmoudi M, Wang Z, Wang RM, Ghatei MA, Bloom SR (1999) Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9–39. Diabetes 48(1):86–93CrossRefPubMedGoogle Scholar
  49. 49.
    Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, Hufner M, Schmiegel WH (2002) Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 87(3):1239–1246CrossRefPubMedGoogle Scholar
  50. 50.
    Pyke C, Heller RS, Kirk RK, Orskov C, Reedtz-Runge S, Kaastrup P, Hvelplund A, Bardram L, Calatayud D, Knudsen LB (2014) GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 155(4):1280–1290CrossRefPubMedGoogle Scholar
  51. 51.
    Muscogiuri G, Cignarelli A, Giorgino F, Prodram F, Santi D, Tirabassi G, Balercia G, Modica R, Faggiano A, Colao A (2014) GLP-1: benefits beyond pancreas. J Endocrinol Invest 37:1143–53CrossRefPubMedGoogle Scholar
  52. 52.
    Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W (1993) Preserved incretin activity of glucagon-like peptide 1 [7–36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91(1):301–307CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Nauck M (1996) Therapeutic potential of glucagon-like peptide 1 in type 2 diabetes. Diabet Med 13(9 Suppl 5):S39–S43PubMedGoogle Scholar
  54. 54.
    Nauck MA (2009) Unraveling the science of incretin biology. Am J Med 122(6 Suppl):S3–S10CrossRefPubMedGoogle Scholar
  55. 55.
    Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiol Rev 87(4):1409–1439CrossRefPubMedGoogle Scholar
  56. 56.
    Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35(6):1364–1379CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Deane AM, Rayner CK, Keeshan A, Cvijanovic N, Marino Z, Nguyen NQ, Chia B, Summers MJ, Sim JA, van Beek T et al (2014) The effects of critical illness on intestinal glucose sensing, transporters, and absorption. Crit Care Med 42:57–65CrossRefPubMedGoogle Scholar
  58. 58.
    Kahles F, Meyer C, Mollmann J, Diebold S, Findeisen HM, Lebherz C, Trautwein C, Koch A, Tacke F, Marx N et al (2014) GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering. Diabetes 63(10):3221–3229CrossRefPubMedGoogle Scholar
  59. 59.
    Summers MJ, DI Bartolomeo AE, Zaknic AV, Chapman MJ, Nguyen NQ, Zacharakis B, Rayner CK, Horowitz M, Deane AM (2014) Endogenous amylin and glucagon-like peptide-1 concentrations are not associated with gastric emptying in critical illness. Acta Anaesthesiol Scand 58(2):235–242CrossRefPubMedGoogle Scholar
  60. 60.
    Muscelli E, Mari A, Casolaro A, Camastra S, Seghieri G, Gastaldelli A, Holst JJ, Ferrannini E (2008) Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 57(5):1340–1348CrossRefPubMedGoogle Scholar
  61. 61.
    Nguyen AT, Mandard S, Dray C, Deckert V, Valet P, Besnard P, Drucker DJ, Lagrost L, Grober J (2014) Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: involvement of the GLP-1 pathway. Diabetes 63(2):471–482CrossRefPubMedGoogle Scholar
  62. 62.
    Nielsen ST, Lehrskov-Schmidt L, Krogh-Madsen R, Solomon TP, Lehrskov-Schmidt L, Holst JJ, Moller K (2013) Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers. Diabetes Metab Res Rev 29(8):655–663CrossRefPubMedGoogle Scholar
  63. 63.
    Combes J, Borot S, Mougel F, Penfornis A (2011) The potential role of glucagon-like peptide-1 or its analogues in enhancing glycaemic control in critically ill adult patients. Diabetes Obes Metab 13(2):118–129CrossRefPubMedGoogle Scholar
  64. 64.
    Pinelli NR, Jones MC, Monday LM, Smith Z, Rhoney DH (2012) Exogenous glucagon-like peptide-1 for hyperglycemia in critically ill patients. Ann Pharmacother 46(1):124–129CrossRefPubMedGoogle Scholar
  65. 65.
    Meier JJ, Weyhe D, Michaely M, Senkal M, Zumtobel V, Nauck MA, Holst JJ, Schmidt WE, Gallwitz B (2004) Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes. Crit Care Med 32(3):848–851CrossRefPubMedGoogle Scholar
  66. 66.
    Sokos GG, Bolukoglu H, German J, Hentosz T, Magovern GJ Jr, Maher TD, Dean DA, Bailey SH, Marrone G, Benckart DH et al (2007) Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am J Cardiol 100(5):824–829CrossRefPubMedGoogle Scholar
  67. 67.
    Deane AM, Summers MJ, Zaknic AV, Chapman MJ, Fraser RJ, Di Bartolomeo AE, Wishart JM, Horowitz M (2011) Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes. Crit Care 15(1):R35CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Deane AM, Chapman MJ, Fraser RJ, Summers MJ, Zaknic AV, Storey JP, Jones KL, Rayner CK, Horowitz M (2010) Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: relationship to glycemia. Crit Care Med 38(5):1261–1269CrossRefPubMedGoogle Scholar
  69. 69.
    Deane AM, Chapman MJ, Fraser RJ, Burgstad CM, Besanko LK, Horowitz M (2009) The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study. Crit Care 13(3):R67CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Galiatsatos P, Gibson BR, Rabiee A, Carlson O, Egan JM, Shannon RP, Andersen DK, Elahi D (2014) The glucoregulatory benefits of glucagon-like peptide-1 (7–36) amide infusion during intensive insulin therapy in critically ill surgical patients: a pilot study. Crit Care Med 42(3):638–645CrossRefPubMedGoogle Scholar
  71. 71.
    Abuannadi M, Kosiborod M, Riggs L, House JA, Hamburg MS, Kennedy KF, Marso SP (2013) Management of hyperglycemia with the administration of intravenous exenatide to patients in the cardiac intensive care unit. Endocr Pract 19(1):81–90CrossRefPubMedGoogle Scholar
  72. 72.
    Mecott GA, Herndon DN, Kulp GA, Brooks NC, Al-Mousawi AM, Kraft R, Rivero HG, Williams FN, Branski LK, Jeschke MG (2010) The use of exenatide in severely burned pediatric patients. Crit Care 14(4):R153CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Meier JJ, Gallwitz B, Siepmann N, Holst JJ, Deacon CF, Schmidt WE, Nauck MA (2003) Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia 46(6):798–801CrossRefPubMedGoogle Scholar
  74. 74.
    Deacon CF, Ahren B (2011) Physiology of incretins in health and disease. Rev Diabet Stud 8(3):293–306CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Zhou J, Livak MF, Bernier M, Muller DC, Carlson OD, Elahi D, Maudsley S, Egan JM (2007) Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets. Am J Physiol Endocrinol Metab 293(2):E538–E547CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Hojberg PV, Vilsboll T, Rabol R, Knop FK, Bache M, Krarup T, Holst JJ, Madsbad S (2009) Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 52(2):199–207CrossRefPubMedGoogle Scholar
  77. 77.
    Layon AJ, Florete OG Jr, Day AL, Kilroy RA, James PB, McGuigan JE (1991) The effect of duodenojejunal alimentation on gastric pH and hormones in intensive care unit patients. Chest 99(3):695–702CrossRefPubMedGoogle Scholar
  78. 78.
    Lee MY, Fraser JD, Chapman MJ, Sundararajan K, Umapathysivam MM, Summers MJ, Zaknic AV, Rayner CK, Meier JJ, Horowitz M et al (2013) The effect of exogenous glucose-dependent insulinotropic polypeptide in combination with glucagon-like peptide-1 on glycemia in the critically ill. Diabetes Care 36(10):3333–3336CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Kar P, Cousins CE, Annink CE, Jones KL, Chapman MJ, Meier JJ, Nauck MA, Horowitz M, Deane AM (2015) Effects of glucose-dependent insulinotropic polypeptide on gastric emptying, glycaemia and insulinaemia during critical illness: a prospective, double blind, randomised, crossover study. Crit Care 19(1):20CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Kar P, Jones KL, Horowitz M, Chapman MJ, Deane AM (2015) Measurement of gastric emptying in the critically ill. Clin Nutr 34(4):557–564CrossRefPubMedGoogle Scholar
  81. 81.
    Dube PE, Brubaker PL (2007) Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators. Am J Physiol Endocrinol Metab 293(2):E460–E465CrossRefPubMedGoogle Scholar
  82. 82.
    Wallis K, Walters JR, Forbes A (2007) Review article: glucagon-like peptide 2--current applications and future directions. Aliment Pharmacol Ther 25(4):365–372CrossRefPubMedGoogle Scholar
  83. 83.
    Estall JL, Drucker DJ (2006) Glucagon-like Peptide-2. Annu Rev Nutr 26:391–411CrossRefPubMedGoogle Scholar
  84. 84.
    Scott RB, Kirk D, MacNaughton WK, Meddings JB (1998) GLP-2 augments the adaptive response to massive intestinal resection in rat. Am J Physiol 275(5 Pt 1):G911–G921PubMedGoogle Scholar
  85. 85.
    Boushey RP, Yusta B, Drucker DJ (1999) Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis. Am J Physiol 277(5 Pt 1):E937–E947PubMedGoogle Scholar
  86. 86.
    Kouris GJ, Liu Q, Rossi H, Djuricin G, Gattuso P, Nathan C, Weinstein RA, Prinz RA (2001) The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis. Am J Surg 181(6):571–575CrossRefPubMedGoogle Scholar
  87. 87.
    Prasad R, Alavi K, Schwartz MZ (2000) Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion. J Pediatr Surg 35(2):357–359CrossRefPubMedGoogle Scholar
  88. 88.
    Cameron HL, Perdue MH (2005) Stress impairs murine intestinal barrier function: improvement by glucagon-like peptide-2. J Pharmacol Exp Ther 314(1):214–220CrossRefPubMedGoogle Scholar
  89. 89.
    Wilhelm SM, Lipari M, Kulik JK, Kale-Pradhan PB (2014) Teduglutide for the treatment of short bowel syndrome. Ann Pharmacother 48(9):1209–1213CrossRefPubMedGoogle Scholar
  90. 90.
    Hernandez G, Velasco N, Wainstein C, Castillo L, Bugedo G, Maiz A, Lopez F, Guzman S, Vargas C (1999) Gut mucosal atrophy after a short enteral fasting period in critically ill patients. J Crit Care 14(2):73–77CrossRefPubMedGoogle Scholar
  91. 91.
    Deitch EA (1990) The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure. Arch Surg 125(3):403–404CrossRefPubMedGoogle Scholar
  92. 92.
    Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR (1985) Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89(5):1070–1077PubMedGoogle Scholar
  93. 93.
    Lin HC, Chey WY, Zhao X (2000) Release of distal gut peptide YY (PYY) by fat in proximal gut depends on CCK. Peptides 21(10):1561–1563CrossRefPubMedGoogle Scholar
  94. 94.
    Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR (2003) Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 349(10):941–948CrossRefPubMedGoogle Scholar
  95. 95.
    Nematy M, O'Flynn JE, Wandrag L, Brynes AE, Brett SJ, Patterson M, Ghatei MA, Bloom SR, Frost GS (2006) Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study. Crit Care 10(1):R10CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Nguyen NQ, Fraser RJ, Bryant LK, Chapman MJ, Wishart J, Holloway RH, Butler R, Horowitz M (2007) The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients. Crit Care 11(6):R132CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Mark P. Plummer
    • 1
    Email author
  • Annika Reintam Blaser
    • 2
  • Adam M. Deane
    • 1
    • 3
  1. 1.Discipline of Acute Care MedicineUniversity of AdelaideAdelaideAustralia
  2. 2.Department of Anaesthesiology and Intensive CareUniversity of TartuTartuEstonia
  3. 3.Department of Critical Care ServicesRoyal Adelaide HospitalAdelaideAustralia

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