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Review: Enteroendocrine cells: Neglected players in gastrointestinal disorders?

Department of Gastroenterology, University Hospital of North Staffordshire, Stoke-on-Trent, UK

Fiona C. Leslie

Department of Gastroenterology, University Hospital of North Staffordshire, Stoke-on-Trent, UK

Scott E. Levison

Gastrointestinal Sciences, University of Manchester, Manchester, UK

John T. McLaughlin

Gastrointestinal Sciences, University of Manchester, Manchester, UK, john.mclaughlin@ manchester.ac.uk

Enteroendocrine cells (EEC) form the basis of the largest endocrine system in the body. They secrete multiple regulatory molecules which control physiological and homeostatic functions, particularly postprandial secretion and motility. Their key purpose is to act as sensors of luminal contents, either in a classical endocrine fashion, or by a paracrine effect on proximate cells, notably vagal afferent fibres. They also play a pivotal role in the control of food intake, and emerging data add roles in mucosal immunity and repair. We propose that EEC are fundamental in several gastrointestinal pathologies, notably Post-infectious Irritable Bowel Syndrome, infectious enteritis, and possibly inflammatory bowel disease. Further work is needed to fully illustrate the importance, detailed biology and therapeutic potential of these frequently overlooked cells.

Key Words: Enteroendocrine cells • innate immunity • inflammation • inflammatory bowel disease • irritable bowel syndrome • anendocrinosis

References

• Al Khalidi, H., Kandel, G. and Streutker, C.J. (2006) Enteropathy with loss of enteroendocrine and paneth cells in a patient with immune dysregulation: a case of adult autoimmune enteropathy . Hum Pathol 37(3): 373-376.[CrossRef][Medline] [Order article via Infotrieve]
• Alverdy, J. and Aoys, E. (1991) The effect of glucocorticoid administration on bacterial translocation. Evidence of an acquired mucosal immunodeficient state . Ann Surg 214(6): 719-723.[Medline] [Order article via Infotrieve]
• Alverdy, J., Stern, E., Poticha, S., Baunoch, D. and Adrian, T. (1997) Cholecystokinin modulates mucosal immunoglobulin A function . Surgery 122(2): 286-292.
• Baynes, K.C., Dhillo, W.S. and Bloom, S.R. (2006) Regulation of food intake by gastrointestinal hormones . Curr Opin Gastroenterol 22(6): 626-631.[Medline] [Order article via Infotrieve]
• Bishop, A., Pietroletti, R., Taat, C., Brummelkamp, W. and Polak, J. (1987) Increased populations of endocrine cells in Crohn's ileitis . Virchows Arch A 410: 391-396.[CrossRef]
• Bjerknes, M. and Cheng, H. (2006) Neurogenin 3 and eteroendocrine cell lineage in the adult mouse small intestinal epithelium . Dev Biol 300(2): 722-735.[CrossRef][Medline] [Order article via Infotrieve]
• Bogunovic, M., Dave, S., Tilstra, J., Chang, D., Harpaz, N., Xiong, H. et al. (2007) Enteroendocrine cells express functional Toll-like receptors . Am J Physiol Gastrointest Liver Physiol 292: 1783 .
• Bozkurt, A., Oktar, B., Kurtel, H., Alican, I., Coskun, T. and Yegen, B. (1999) Capsaicin-sensitive vagal fibres and 5-HT3-gastrin releasing peptide- and cholecystokinin A-receptors are involved in distension-induced inhibition of gastric emptying in the rat . Regul Pept 83(2-3): 81-86.[CrossRef][Medline] [Order article via Infotrieve]
• Bulut, K., Meier, J.J., Ansorge, N., Feiderbauer, P., Schmitz, F., Hoffmann, P. et al. (2004) Glucagon-like peptide 2 improves intestinal wound healing through induction of epithelial cell migration in vitro-evidence for a TGF-beta mediated effect . Regul Pept 121(1-3): 137-143.[CrossRef][Medline] [Order article via Infotrieve]
• Cameron, H. and Perdue, M. (2005) Stress impairs murine type Intestinal Barrier Function: Improvement by Glucagon-like peptide-2 . J Pharmacol and Experiment Therapeuthic 314: 214-220.[CrossRef]
• Cameron, H., Yang, P.-C. and Perdue, M. (2003) Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy . Am J Physiol Gastroint Liver Physiol 284: G905-G912.[Abstract/Free Full Text]
• Chan, J., Gonsalkorale, W., Perrey, C., Previca, V., Hajeer, A., Whorwell, P. et al. (2000) IL-10 and TGF-B genotypes in Irritable bowel syndrome: Evidence to support and inflamatory component . Gastroenterology 118(4): 184 .
• Chua, A., Dinan, T., Rovati, L. and Keeling, P. (1994) Cholecystokinin hyperresponsiveness in Dysmotility-Type nonulcer Dyspepsia . Annals of the New York Academ Sci 713(1): 298-299.[CrossRef]
• Cortina, G., Smart, Cn., Farmer, D.G., Bhuta, S., Treem, W.R. and Hill, I.D. (2007) Enteroendocrine cell dysgenesis and malabsorption, a histologic and immunohistochemical characterization . Human Pathol 38(4): 570-580.[CrossRef][Medline] [Order article via Infotrieve]
• Cubeddu, L., Hoffmann, I., Feunmayor, N. and Finn, A. (1990) Efficacy of Ondansetron (GR 38032F) and he role of serotonin in cisplatininduced nausea and vomiting . N Eng J Med 322(12): 810-816.[Abstract]
• Cummings, D. and Overduin, J. (2007) Gastrointestinal regulation of food intake . The J Clin Invest 117(1).
• Deprez, P., Sempoux, C., De Saeger, C., Rahier, J., Mainguet, P., Pauwels, S., et al. (2002) Expression of cholecystokinin in the duodenum of patients with coeliac disease: respective role of atrophy and lymphocytic infiltration . Clin Sci ( Lond ) 103(2): 171-77.[Medline] [Order article via Infotrieve]
• Desai, S., Loomis, Z., Pugh-Bernard, A., Schrunk, J., Doyle, M., Minic, A., et al. (2008) Nkx2.2 regulates cell fate choice in the enteroendocrine cell lineages of the intestine . Dev Biol 313(1): 58-66.[CrossRef][Medline] [Order article via Infotrieve]
• Dockray, G., Desmond, H., Gayton, R., Jonsson, A., Raybould, H., Sharkey, K.A. et al. (1985) Cholecystokinin and gastrin forms in the nervous system . Ann N Y Acad Sci 448: 32-43.[CrossRef][Medline] [Order article via Infotrieve]
• Drucker, D. (2006) The biology of incretin hormones . Cell Metab 3(3): 153-165.[CrossRef][Medline] [Order article via Infotrieve]
• Dunlop, S.P., Jenkins, D., Neal, K. and Spiller, R. (2003) Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS . Gastroenterology 125(6): 1651-1659.[CrossRef][Medline] [Order article via Infotrieve]
• Dynes, R., Poppi, D., Barrell, G. and Sykes, A. (1998) Elevation of food intake in parasite-infected lambs by central administration of a cholecystokinin receptor antagonist . Br J Nutrition 79(1): 47-54.[CrossRef][Medline] [Order article via Infotrieve]
• El-Salhy, M., Danielsson, A., Stenling, R. and Grimelius, L. (1997) Colonic endocrine cells in Inflammatory Bowel Disease . J Intern Med 242(5): 413-419.[CrossRef][Medline] [Order article via Infotrieve]
• Freier, S., Eran, M., Alon, I. and Elath, U. (1991) Verapamil and frsemide prevent cholecystokinin-induced tanslocation of immunoglobulins in rat intestine . Dig Dis Sci 36(11): 1619-1624.[CrossRef][Medline] [Order article via Infotrieve]
• Freier, S., Eran, M. and Alon, I. (1989) A study of stimuli operative in the release of antibodies in the rat intestine . Immunol Invest 18(1-4): 431-437.[CrossRef][Medline] [Order article via Infotrieve]
• Furness, J.B., Kunze, W. and Clerc, N. (1999) Nutrient tasting and signalling mechanisms in the gut II. The intestine as a sensory organ: neural, endocrine, and immune responses . Am J Physiol Gastrointest Liver Physiol 277: G922-G928.[Abstract/Free Full Text]
• Gee, M., Grace, M., Wensel, R., Sherbaniuk, R. and Thomson, A. (1985) Protein energy malnutrition in gastroenterology outpatients:increased risk in Crohn's disease . J Am Diet Assoc 85(11): 1466-1474.[Medline] [Order article via Infotrieve]
• Gibbs, J., Young, R. and Smith, G. (1973) Cholecystokinin elicits satiety in rats with open gastric fistulas . Nature 245: 323-325.[CrossRef][Medline] [Order article via Infotrieve]
• Grundy, D., Bagaev, V. and Hillsley, K. (1995) Inhibition of gastric mechanoreceptor discharge by cholecystokinin in the rat . Am J Physiol 268(2 Pt 1): 355-360.
• Keith Hanna, M., Zarzaur, B., Fukatsu, K., DeWitt, R., Renegar, K., Sherrell, C. et al. (2000) Individual neuropeptides regulate gut-associated lymphoid tissue integrity, intestinal immunoglobin A levels, and respiratory antibacterial immunity . J Parenter and Enter nutr 24(5): 261-268.[CrossRef]
• Hogenauer, C., Meyer, R., Netto, G., Bell, D., Little, K., Ferries, L. et al. (2001) Malabsorption due to cholecystokinin deficiency in a patient with autoimmune polyglandular syndrome type 1 . The New England J Med 344(4): 270-274.[CrossRef]
• Houghton, L., Atkinson, W., Whitaker, R. and Whorwell, P. (2003) Increased platelet depleted plasma 5-hydoxytryptamine following meal ingestion in symptomatic female subjects in predominant irritable bowel syndrome . Gut 52(5): 663-670.[Abstract/Free Full Text]
• Imaeda, H., Miura, S., Serizawa, H., Toda, K., Ohkubo, N. and Kimura, H. (1993) Influence of fatty acid absorption on bidirectional release of immunoglobulin A into the intestinal lumen and intestinal lymp in rats . Immuno Lett 38(3): 253-258.[CrossRef]
• Lal, S., McLaughlin, J., Barlow, J., D'Amato, M., Giacovelli, G. and Varro, A. (2004) Cholecystokinin pathways modulate sensations induced by gastric distension in humans . Am J Phsiol Gastroint Liver Physiol 287(1): 72-79.[CrossRef]
• Le Roux, C., Aylwin, S., Batterham, R., Borg, C., Coyle, F., Prasad, V. et al. (2006) Gut hormone profiles following bariatric surgery favor a anorectic state, facilitate weigh loss, and improve metabolic parameters . Ann Surg 243(1): 108-114.[CrossRef][Medline] [Order article via Infotrieve]
• Le Roux, C., Borg, C., Murphy, K., Vincent, R., Ghatel, M. and Bloom, S. (2008) Supraphysiological doses of intravenous PYY(3-36) cause nausea, but no additional reduction in food intake . Ann Clin Biochem 45(1): 93-95.[Abstract/Free Full Text]
• Lee, C., Perreault, N., Brestelli, J. and Kaestner, K. (2002) Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity . Genes and Develop 16(12): 1488-1497.[Abstract/Free Full Text]
• Leslie, FC, Thompson, D., McLaughlin, J., Varro, A., Dockray, G. and Mandal, B. (2003) Plasma cholecystokinin concentrations are elevated in acute upper gastrointestinal infections . Q J Med 96: 870-871.
• Linden, D., Chen, J.-X., Gershon, M., Sharkey, K. and Mawe, G. (2003) Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis . Am J Physiol Gastroint Liver Physiol 285: G207-G216.[Abstract/Free Full Text]
• Liu, X., Nelson, D., Holst, J. and Ney, D. (2006) Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome . Am J Clin Nutri 84: 1142-1150.[Abstract/Free Full Text]
• Longstreath, G., Hawkey, C., Ham, J., Jones, R., Mayer, E., Naesdal, J. et al. (2000) Demographic and clinical characteristics of patients with irritable bowel syndrome (IBS) from three practice settings; Gastroenterology 118(4): A146 .
• Lovshin, J. and Drucker, D. (2000) New frontiers in the biology of GLP-2 . Regulatory Peptides 90(1-3): 27-32.[CrossRef][Medline] [Order article via Infotrieve]
• Luyer, M., Greve, J., Hadfoune, M., Dejing, C. and Buurman, W. (2005) Nutritional stimulation of cholecystokinin receptorsinhibits inflammation via the vagus . J Exp Med 202(8): 1023-1029.[Abstract/Free Full Text]
• Martin, G., Beck, P. and Sigalet, D. (2006) Gut hormones, and short bowel syndrome: The enigmatic role of glucaon-like peptide-2 in the regulation of intestinal adaptation . World J Gastroenterol 12(26): 4117-4129Review.[Medline] [Order article via Infotrieve]
• Matzinger, D., Degen, L., Drewe, J., Duebendorfer, R., Ruckstuhl, N. and D'Amato, M. (2000) The role of long chain fatty acids in regulating food intake and cholecystokinin release in humans . Gut 46: 689-694.[Abstract/Free Full Text]
• Matzinger, D., Gutzwiller, J., Drewe, J., Orban, A., Engel, R. and D'Amato, M. (1999) Inhibition of food intake in response to intestinal lipid is mediated by cholecystokinin in humans . Am J Phsiol 277(6 Pt 2): R1718-1724.[Medline] [Order article via Infotrieve]
• McDermott, J.R., Leslie, F., D'Amato, M., Thompson, D., Grencis, R. and McLaughlin, J. (2006) Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation . Gut 55: 492-497.[Abstract/Free Full Text]
• McHugh, K., Castonguay, T., Collins, S. and Weingarten, H. (1993) Characterisation of suppression of food intake following acute colon inflammation in the rat . Am J Physiol Regul Integr Comp Physiol 265: R1001-R1005.[Abstract/Free Full Text]
• Moran, T. and Bi, S. (2006) Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: developmental aspects . Dev Psychobiol 48(5): 360-367.[CrossRef][Medline] [Order article via Infotrieve]
• Moran, T., Katz, L., Plata-Salaman, C. and Schwartz, G. (1998) Disordered food intake and obesity in rats lacking cholecustokinin A receptors . Am J Physiol Regu Integr Comp Physiol 274: R618-R625.[Abstract/Free Full Text]
• O'Hara, J., Ho, W., Linden, D., Mawe, G. and Sharkey, K. (2004) Enteroendocrine cells and 5-HT availability in mucosa of guinea pigs with TNBS ileitis . Am J Physiol Gastrointest Liver Physiol 287: G998-G1007.[Abstract/Free Full Text]
• Oshima, S., Fujimura, M. and Fukimiya, M. (1999) Changes in the number of serotonin-containing cell and serotonin levels in the intestinal mucosa of rats with colitis induced by dextran sodium sulphate . Histochem and Cell Biol 112(4).
• Otte, J., Cario, E. and Podolsky, D. (2004) Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells . Gastroenterology 126(4): 1054-1070.[CrossRef][Medline] [Order article via Infotrieve]
• Palazzo, M., Balsari, A., Rossini, A., Selleri, S., Calcaterra, C., Gariboldi, S. et al. (2007) Activation of enteroendocrine cells via TLRs induces hormone, chemokine, and defensin secretion . The J Immunol 178: 4296-4303.
• Patti, M., McMahon, G., Mun, E., Bitton, A., Holst, J. et al. (2005) Severe Hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence of inappropriate insulin secretion and pancreatic islet cell hyperplasia . Diabetologia 48: 2236-2240.[CrossRef][Medline] [Order article via Infotrieve]
• Pironi, L., Stanghellini, V., Miglioli, M., Corinaldesi, R., De Giorgio, R., Ruggeri, E. et al. (1993) Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY . Gastroenterology 105(3): 733-739.[Medline] [Order article via Infotrieve]
• Rigaud, D., Angel, L., Cerf, M., Carduner, M., Melchior, J.-C., Sautier, C. et al. (1994) Mechnisms of decreased food intake during weight loss in ault Crohn's disease patients without obvious malabsorption . Am J Clin Nutrition 60: 775-781.[Abstract/Free Full Text]
• Rioux, J., Xavier, R., Taylor, K., Silverberg, M., Goyette, P. and Huett, A. (2007) Genome-wide association study identifies new susceptibility loci for Crohn's disease an implicates autophagy in disease pathogenesis . Nature Genet 39(5).
• Rubin, D., Zhang, H., Qian, P., Lorenz, R., Hutton, K. and Peters, M. (2000) Altered Enteroendocrine Cell Expression in T cell Receptor Alpha Chain Knock-Out Mice . Microscopy Res and Tech 51: 112-120.[CrossRef]
• Sakiyama, T., Fujita, H. and Tsubouchi, H. (2007) Autoantibodies against ubiquitination factor E4A (UBE4A) are associated with severity of Crohn's disease . Inflamm Bowel Dis 14(3): 310-317.[CrossRef]
• Sarson, DL (1981) Gut hormone changes after jejunoileal or biliopancreatic bypass surgery for morbid obesity . Int J Obes 5: 471-480.[Medline] [Order article via Infotrieve]
• Skipper, M. and Lewis, J. (2000) Getting to the Guts of enteroendocrine differentiation . Nature Genet 24: 3-4.[CrossRef][Medline] [Order article via Infotrieve]
• Sood, A., Midha, V., Sood, N., Bansal, M., Kaur, M., Goyal, A. et al. (2007) Coexistence of chronic calcific pancreatitis and celiac disease . Indian J Gastroenterol 26(1): 41-42.[Medline] [Order article via Infotrieve]
• Spiller, R. (2003) Postinfectious irritable bowel syndrome . Gastroenterology 124(6): 1662-1671.[CrossRef][Medline] [Order article via Infotrieve]
• Spiller, RC, Jenkins, D., Thornley, J., Hebden, J., Wright, T., Skinner, M. et al. (2000) Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome . Gut 47: 804-811.[Abstract/Free Full Text]
• Sternini, C., Anselmi, L. and Rozengurt, E. (2008) Enteroendocrine, cells: a site of `taste' in gastrointestinal chemosensing . Curr Opin Endocrinol Diabetes Obes 15(1): 73-78.[Medline] [Order article via Infotrieve]
• Takeda, K. and Akira, S. (2005) Toll like receptors in innate immunity . Int Immunol 17(1): 1-14.[Abstract/Free Full Text]
• Tracey, K. (2005) Fat meets cholinergic antiinflammatory pathway . JEM 202(8): 1017-1021.[Abstract/Free Full Text]
• Wang, H., Steeds, J., Motomura, Y., Deng, Y., Verma-Gandhu, M., El-Sharkwawy, R. et al. (2007) CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection . Gut 56: 949-957.[Abstract/Free Full Text]
• Wheatcroft, J., Wakelin, D., Smith, A., Mahoney, C., Mawe, G. and Spiller, R. (2005) Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction . Neurogastroenterol Motil 17(6): 863-870.[CrossRef][Medline] [Order article via Infotrieve]
• Wortley, K., Del Rincon, J.P., Murray, J., Garcia, K., Iida, K. and Thorner, M. (2005) Absence of ghrelin protects against early-onset obesity . J Clin Invest 115(12): 3573-3578.[CrossRef][Medline] [Order article via Infotrieve]
• Yamada, S., Kojima, H., Fujimiya, M., Nakamura, T., Kashiwagi, A. and Kikkawa, R. (2001) Differentiation of immature enterocytes in enteroendocrine cells by Pdx1 overexpression . Am J Physiol Gastrointest. Liver Physiol 281: G229-G236.[Abstract/Free Full Text]
• Yang, Qi., Bermingham, N., Finegold, M. and Zoghbi, H. (2001) Requirement of Math1 for secretory cell lineae commitment in the mouse intestine . Science 294(5549): 2155-2158.[Abstract/Free Full Text]
• Yang, S., Gaafar, S. and Bottoms, G. (1990) Serum levels of gastrin, insulin and glucagon as possible factors of anorexia in pigs infected once with ascaris suum . Vet Parasitol 36(3-4): 211-219.[CrossRef][Medline] [Order article via Infotrieve]
• Zigman, J., Nakano, Y., Coppari, R., Balthasar, N., Marcus, J. and Lee, C. (2005) Mice lacking ghrelin receptors resist the development of diet-induced obesity . J Clin Invest 115(12): 3564-3572.[CrossRef][Medline] [Order article via Infotrieve]

Therapeutic Advances in Gastroenterology, Vol. 1, No. 1, 51-60 (2008)
DOI: 10.1177/1756283X08093943


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Moran, G. W. Articles by McLaughlin, J. T. Search for Related Content Social Bookmarking                         What's this?