1932

Abstract

The enteroendocrine system orchestrates how the body responds to the ingestion of foods, employing a diversity of hormones to fine-tune a wide range of physiological responses both within and outside the gut. Recent interest in gut hormones has surged with the realization that they modulate glucose tolerance and food intake through a variety of mechanisms, and such hormones are therefore excellent therapeutic candidates for the treatment of diabetes and obesity. Characterizing the roles and functions of different enteroendocrine cells is an essential step in understanding the physiology, pathophysiology, and therapeutics of the gut-brain-pancreas axis.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-021115-105439
2016-02-10
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/physiol/78/1/annurev-physiol-021115-105439.html?itemId=/content/journals/10.1146/annurev-physiol-021115-105439&mimeType=html&fmt=ahah

Literature Cited

  1. Sjölund K, Sandén G, Håkanson R, Sundler F. 1.  1983. Endocrine cells in human intestine: an immunocytochemical study. Gastroenterology 85:1120–30 [Google Scholar]
  2. Stengel A, Taché Y. 2.  2009. Regulation of food intake: the gastric X/A-like endocrine cell in the spotlight. Curr. Gastroenterol. Rep. 11:448–54 [Google Scholar]
  3. Håkanson R, Böttcher G, Ekblad E, Panula P, Simonsson M. 3.  et al. 1986. Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies. Histochemistry 86:5–17 [Google Scholar]
  4. Lamberts R, Stumps D, Plümpe L, Creutzfeldt W. 4.  1991. Somatostatin cells in rat antral mucosa: qualitative and quantitative ultrastructural analyses in different states of gastric acid secretion. Histochemistry 95:373–82 [Google Scholar]
  5. Ku SK, Lee HS, Lee JH. 5.  2003. An immunohistochemical study of the gastrointestinal endocrine cells in the C57BL/6 mice. Anat. Histol. Embryol. 32:21–28 [Google Scholar]
  6. Itoh Z. 6.  1997. Motilin and clinical application. Peptides 18:593–608 [Google Scholar]
  7. Grosse J, Heffron H, Burling K, Akhter Hossain M, Habib AM. 7.  et al. 2014. Insulin-like peptide 5 is an orexigenic gastrointestinal hormone. PNAS 111:11133–38 [Google Scholar]
  8. Habib AM, Richards P, Cairns LS, Rogers GJ, Bannon CA. 8.  et al. 2012. Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology 153:3054–65 [Google Scholar]
  9. Egerod KL, Engelstoft MS, Grunddal KV, Nohr MK, Secher A. 9.  et al. 2012. A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Endocrinology 153:5782–95 [Google Scholar]
  10. Svendsen B, Pedersen J, Albrechtsen NJ, Hartmann B, Toräng S. 10.  et al. 2015. An analysis of cosecretion and coexpression of gut hormones from male rat proximal and distal small intestine. Endocrinology 156:847–57 [Google Scholar]
  11. Cho HJ, Kosari S, Hunne B, Callaghan B, Rivera LR. 11.  et al. 2015. Differences in hormone localisation patterns of K and L type enteroendocrine cells in the mouse and pig small intestine and colon. Cell Tissue Res. 359:693–98 [Google Scholar]
  12. Theodorakis MJ, Carlson O, Michopoulos S, Doyle ME, Juhaszova M. 12.  et al. 2006. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am. J. Physiol. Endocrinol. Metab. 290:E550–59 [Google Scholar]
  13. Bohórquez DV, Samsa LA, Roholt A, Medicetty S, Chandra R, Liddle RA. 13.  2014. An enteroendocrine cell–enteric glia connection revealed by 3D electron microscopy. PLOS ONE 9:e89881 [Google Scholar]
  14. Bohórquez DV, Chandra R, Samsa LA, Vigna SR, Liddle RA. 14.  2011. Characterization of basal pseudopod-like processes in ileal and colonic PYY cells. J. Mol. Histol. 42:3–13 [Google Scholar]
  15. Chandra R, Samsa LA, Vigna SR, Liddle RA. 15.  2010. Pseudopod-like basal cell processes in intestinal cholecystokinin cells. Cell Tissue Res. 341:289–97 [Google Scholar]
  16. Bohórquez DV, Shahid RA, Erdmann A, Kreger AM, Wang Y. 16.  et al. 2015. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J. Clin. Investig. 125:782–86 [Google Scholar]
  17. Pearse AG, Polak JM. 17.  1971. Neural crest origin of the endocrine polypeptide (APUD) cells of the gastrointestinal tract and pancreas. Gut 12:783–88 [Google Scholar]
  18. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M. 18.  et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–7 [Google Scholar]
  19. Gerbe F, Legraverend C, Jay P. 19.  2012. The intestinal epithelium tuft cells: specification and function. Cell. Mol. Life Sci. 69:2907–17 [Google Scholar]
  20. Neutra MR. 20.  1998. Current concepts in mucosal immunity. V. Role of M cells in transepithelial transport of antigens and pathogens to the mucosal immune system. Am. J. Physiol. Gastrointest. Liver Physiol. 274:G785–91 [Google Scholar]
  21. Madara JL. 21.  1982. Cup cells: structure and distribution of a unique class of epithelial cells in guinea pig, rabbit, and monkey small intestine. Gastroenterology 83:981–94 [Google Scholar]
  22. Sei Y, Lu X, Liou A, Zhao X, Wank SA. 22.  2011. A stem cell marker–expressing subset of enteroendocrine cells resides at the crypt base in the small intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 300:G345–56 [Google Scholar]
  23. Cheng H, Leblond CP. 23.  1974. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. III. Entero-endocrine cells. Am. J. Anat. 141:503–19 [Google Scholar]
  24. Thompson EM, Price YE, Wright NA. 24.  1990. Kinetics of enteroendocrine cells with implications for their origin: a study of the cholecystokinin and gastrin subpopulations combining tritiated thymidine labelling with immunocytochemistry in the mouse. Gut 31:406–11 [Google Scholar]
  25. Tsubouchi S, Leblond CP. 25.  1979. Migration and turnover of entero-endocrine and caveolated cells in the epithelium of the descending colon, as shown by radioautography after continuous infusion of 3H-thymidine into mice. Am. J. Anat. 156:431–51 [Google Scholar]
  26. Lehy T, Willems G. 26.  1976. Population kinetics of antral gastrin cells in the mouse. Gastroenterology 71:614–19 [Google Scholar]
  27. Zac-Varghese S, Trapp S, Richards P, Sayers S, Sun G. 27.  et al. 2014. The Peutz-Jeghers kinase LKB1 suppresses polyp growth from intestinal cells of a proglucagon-expressing lineage in mice. Dis. Model. Mech. 7:1275–86 [Google Scholar]
  28. Jenny M, Uhl C, Roche C, Duluc I, Guillermin V. 28.  et al. 2002. Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium. EMBO J. 21:6338–47 [Google Scholar]
  29. Li HJ, Ray SK, Singh NK, Johnston B, Leiter AB. 29.  2011. Basic helix-loop-helix transcription factors and enteroendocrine cell differentiation. Diabetes Obes. Metab. 13:Suppl. 15–12 [Google Scholar]
  30. May CL, Kaestner KH. 30.  2010. Gut endocrine cell development. Mol. Cell. Endocrinol. 323:70–75 [Google Scholar]
  31. López-Díaz L, Jain RN, Keeley TM, VanDussen KL, Brunkan CS. 31.  et al. 2007. Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate. Dev. Biol. 309:298–305 [Google Scholar]
  32. Wang J, Cortina G, Wu SV, Tran R, Cho JH. 32.  et al. 2006. Mutant neurogenin-3 in congenital malabsorptive diarrhea. N. Engl. J. Med. 355:270–80 [Google Scholar]
  33. Servitja JM, Ferrer J. 33.  2004. Transcriptional networks controlling pancreatic development and beta cell function. Diabetologia 47:597–613 [Google Scholar]
  34. Li HJ, Johnston B, Aiello D, Caffrey DR, Giel-Moloney M. 34.  et al. 2014. Distinct cellular origins for serotonin-expressing and enterochromaffin-like cells in the gastric corpus. Gastroenterology 146:754–64.e3 [Google Scholar]
  35. Walker AK, Park WM, Chuang JC, Perello M, Sakata I. 35.  et al. 2013. Characterization of gastric and neuronal histaminergic populations using a transgenic mouse model. PLOS ONE 8:e60276 [Google Scholar]
  36. Reimann F, Habib AM, Tolhurst G, Parker HE, Rogers GJ, Gribble FM. 36.  2008. Glucose sensing in L cells: a primary cell study. Cell Metab. 8:532–39 [Google Scholar]
  37. Hayashi Y, Yamamoto M, Mizoguchi H, Watanabe C, Ito R. 37.  et al. 2009. Mice deficient for glucagon gene–derived peptides display normoglycemia and hyperplasia of islet α-cells but not of intestinal L-cells. Mol. Endocrinol. 23:1990–99 [Google Scholar]
  38. Parker HE, Habib AM, Rogers GJ, Gribble FM, Reimann F. 38.  2009. Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells. Diabetologia 52:289–98 [Google Scholar]
  39. Suzuki K, Harada N, Yamane S, Nakamura Y, Sasaki K. 39.  et al. 2013. Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet–induced obesity. J. Biol. Chem. 288:1929–38 [Google Scholar]
  40. Sykaras AG, Demenis C, Cheng L, Pisitkun T, Mclaughlin JT. 40.  et al. 2014. Duodenal CCK cells from male mice express multiple hormones including ghrelin. Endocrinology 155:3339–51 [Google Scholar]
  41. Sakata I, Nakano Y, Osborne-Lawrence S, Rovinsky SA, Lee CE. 41.  et al. 2009. Characterization of a novel ghrelin cell reporter mouse. Regul. Pept. 155:91–98 [Google Scholar]
  42. Engelstoft MS, Park WM, Sakata I, Kristensen LV, Husted AS. 42.  et al. 2013. Seven transmembrane G protein–coupled receptor repertoire of gastric ghrelin cells. Mol. Metab. 2:376–92 [Google Scholar]
  43. Adriaenssens A, Lam B, Billing L, Skeffington K, Sewing S. 43.  et al. 2015. A transcriptome-led exploration of molecular mechanisms regulating somatostatin-producing D-cells in the gastric epithelium. Endocrinology 1563924–36
  44. Rindi G, Ratineau C, Ronco A, Candusso ME, Tsai M, Leiter AB. 44.  1999. Targeted ablation of secretin-producing cells in transgenic mice reveals a common differentiation pathway with multiple enteroendocrine cell lineages in the small intestine. Development 126:4149–56 [Google Scholar]
  45. Fang R, Olds LC, Sibley E. 45.  2006. Spatio-temporal patterns of intestine-specific transcription factor expression during postnatal mouse gut development. Gene Expr. Patterns 6:426–32 [Google Scholar]
  46. Middendorp S, Schneeberger K, Wiegerinck CL, Mokry M, Akkerman RD. 46.  et al. 2014. Adult stem cells in the small intestine are intrinsically programmed with their location-specific function. Stem Cells 32:1083–91 [Google Scholar]
  47. Jepeal LI, Fujitani Y, Boylan MO, Wilson CN, Wright CV, Wolfe MM. 47.  2005. Cell-specific expression of glucose-dependent-insulinotropic polypeptide is regulated by the transcription factor PDX-1. Endocrinology 146:383–91 [Google Scholar]
  48. Larsson LI, Madsen OD, Serup P, Jonsson J, Edlund H. 48.  1996. Pancreatic-duodenal homeobox 1: role in gastric endocrine patterning. Mech. Dev. 60:175–84 [Google Scholar]
  49. Jepeal LI, Boylan MO, Wolfe MM. 49.  2003. Cell-specific expression of the glucose-dependent insulinotropic polypeptide gene functions through a GATA and an ISL-1 motif in a mouse neuroendocrine tumor cell line. Regul. Pept. 113:139–47 [Google Scholar]
  50. Talchai C, Xuan S, Kitamura T, DePinho RA, Accili D. 50.  2012. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat. Genet. 44:406–12 [Google Scholar]
  51. Sakar Y, Duca FA, Langelier B, Devime F, Blottiere H. 51.  et al. 2014. Impact of high-fat feeding on basic helix-loop-helix transcription factors controlling enteroendocrine cell differentiation. Int. J. Obes. 38:1440–48 [Google Scholar]
  52. Richards P, Pais R, Brighton CE, Habib AM, Yeo GS. 52.  et al. 2015. High fat diet impairs the function of glucagon-like peptide-1 producing L-cells. Peptides In press
  53. Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GM. 53.  et al. 2011. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60:2775–86 [Google Scholar]
  54. Petersen N, Reimann F, Bartfeld S, Farin HF, Ringnalda FC. 54.  et al. 2014. Generation of L-cells in mouse and human small intestine organoids. Diabetes 63:410–20 [Google Scholar]
  55. Wichmann A, Allahyar A, Greiner TU, Plovier H, Lundén G. 55.  et al. 2013. Microbial modulation of energy availability in the colon regulates intestinal transit. Cell Host Microbe 14:582–90 [Google Scholar]
  56. Jørgensen NB, Jacobsen SH, Dirksen C, Bojsen-Møller KN, Naver L. 56.  et al. 2012. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance. Am. J. Physiol. Endocrinol. Metab. 303:E122–31 [Google Scholar]
  57. Peterli R, Steinert RE, Woelnerhanssen B, Peters T, Christoffel-Courtin C. 57.  et al. 2012. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes. Surg. 22:740–48 [Google Scholar]
  58. Mumphrey MB, Patterson LM, Zheng H, Berthoud HR. 58.  2013. Roux-en-Y gastric bypass surgery increases number but not density of CCK-, GLP-1-, 5-HT-, and neurotensin-expressing enteroendocrine cells in rats. Neurogastroenterol. Motil. 25:e70–79 [Google Scholar]
  59. Hansen CF, Bueter M, Theis N, Lutz T, Paulsen S. 59.  et al. 2013. Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats. PLOS ONE 8:e65696 [Google Scholar]
  60. le Roux CW, Borg C, Wallis K, Vincent RP, Bueter M. 60.  et al. 2010. Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation. Ann. Surg. 252:50–56 [Google Scholar]
  61. Drucker DJ, Yusta B. 61.  2014. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annu. Rev. Physiol. 76:561–83 [Google Scholar]
  62. Deloose E, Janssen P, Depoortere I, Tack J. 62.  2012. The migrating motor complex: control mechanisms and its role in health and disease. Nat. Rev. Gastroenterol. Hepatol. 9:271–85 [Google Scholar]
  63. Schubert ML, Peura DA. 63.  2008. Control of gastric acid secretion in health and disease. Gastroenterology 134:1842–60 [Google Scholar]
  64. Vahl TP, Drazen DL, Seeley RJ, D'Alessio DA, Woods SC. 64.  2010. Meal-anticipatory glucagon-like peptide-1 secretion in rats. Endocrinology 151:569–75 [Google Scholar]
  65. Dailey MJ, Stingl KC, Moran TH. 65.  2012. Disassociation between preprandial gut peptide release and food-anticipatory activity. Endocrinology 153:132–42 [Google Scholar]
  66. Schirra J, Katschinski M, Weidmann C, Schäfer T, Wank U. 66.  et al. 1996. Gastric emptying and release of incretin hormones after glucose ingestion in humans. J. Clin. Investig. 97:92–103 [Google Scholar]
  67. Roberge JN, Brubaker PL. 67.  1993. Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. Endocrinology 133:233–40 [Google Scholar]
  68. Rocca AS, Brubaker PL. 68.  1999. Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 140:1687–94 [Google Scholar]
  69. Beglinger S, Drewe J, Schirra J, Göke B, D'Amato M, Beglinger C. 69.  2010. Role of fat hydrolysis in regulating glucagon-like peptide-1 secretion. J. Clin. Endocrinol. Metab. 95:879–86 [Google Scholar]
  70. Hansen L, Holst JJ. 70.  2002. The effects of duodenal peptides on glucagon-like peptide-1 secretion from the ileum. A duodeno–ileal loop?. Regul. Pept. 110:39–45 [Google Scholar]
  71. Palnaes Hansen C, Andreasen JJ, Holst JJ. 71.  1997. The release of gastric inhibitory peptide, glucagon-like peptide-I, and insulin after oral glucose test in colectomized subjects. Scand. J. Gastroenterol. 32:473–77 [Google Scholar]
  72. Cho HJ, Robinson ES, Rivera LR, McMillan PJ, Testro A. 72.  et al. 2014. Glucagon-like peptide 1 and peptide YY are in separate storage organelles in enteroendocrine cells. Cell Tissue Res. 357:63–69 [Google Scholar]
  73. Reimann F, Gribble FM. 73.  2002. Glucose-sensing in glucagon-like peptide-1–secreting cells. Diabetes 51:2757–63 [Google Scholar]
  74. Parker HE, Adriaenssens A, Rogers G, Richards P, Koepsell H. 74.  et al. 2012. Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion. Diabetologia 55:2445–55 [Google Scholar]
  75. Murphy R, Tura A, Clark PM, Holst JJ, Mari A, Hattersley AT. 75.  2009. Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor. Diabetologia 52:154–59 [Google Scholar]
  76. Pearson ER, Flechtner I, Njølstad PR, Malecki MT, Flanagan SE. 76.  et al. 2006. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N. Engl. J. Med. 355:467–77 [Google Scholar]
  77. El-Ouaghlidi A, Rehring E, Holst JJ, Schweizer A, Foley J. 77.  et al. 2007. The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion. J. Clin. Endocrinol. Metab. 92:4165–71 [Google Scholar]
  78. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ. 78.  et al. 2007. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. PNAS 104:15069–74 [Google Scholar]
  79. Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E. 79.  et al. 2007. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. PNAS 104:15075–80 [Google Scholar]
  80. Brown RJ, Rother KI. 80.  2012. Non-nutritive sweeteners and their role in the gastrointestinal tract. J. Clin. Endocrinol. Metab. 97:2597–605 [Google Scholar]
  81. Kuhre RE, Frost CR, Svendsen B, Holst JJ. 81.  2015. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine. Diabetes 64:370–82 [Google Scholar]
  82. Gorboulev V, Schürmann A, Vallon V, Kipp H, Jaschke A. 82.  et al. 2012. Na+-d-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61:187–96 [Google Scholar]
  83. Powell DR, Smith M, Greer J, Harris A, Zhao S. 83.  et al. 2013. LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose. J. Pharmacol. Exp. Ther. 345:250–59 [Google Scholar]
  84. Lindgren O, Carr RD, Deacon CF, Holst JJ, Pacini G. 84.  et al. 2011. Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans. J. Clin. Endocrinol. Metab. 96:2519–24 [Google Scholar]
  85. Edfalk S, Steneberg P, Edlund H. 85.  2008. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57:2280–87 [Google Scholar]
  86. Sykaras AG, Demenis C, Case RM, McLaughlin JT, Smith CP. 86.  2012. Duodenal enteroendocrine I-cells contain mRNA transcripts encoding key endocannabinoid and fatty acid receptors. PLOS ONE 7e42373
  87. Hauge M, Vestmar MA, Husted AS, Ekberg JP, Wright MJ. 87.  et al. 2015. GPR40 (FFAR1)—combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo. Mol. Metab. 4:3–14 [Google Scholar]
  88. Liou AP, Lu X, Sei Y, Zhao X, Pechhold S. 88.  et al. 2011. The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid–induced secretion of cholecystokinin. Gastroenterology 140:903–12 [Google Scholar]
  89. Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K. 89.  et al. 2015. Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion. Endocrinology 156:837–46 [Google Scholar]
  90. Chu ZL, Carroll C, Alfonso J, Gutierrez V, He H. 90.  et al. 2008. A role for intestinal endocrine cell–expressed G protein–coupled receptor 119 in glycemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release. Endocrinology 149:2038–47 [Google Scholar]
  91. Katz LB, Gambale JJ, Rothenberg PL, Vanapalli SR, Vaccaro N. 91.  et al. 2012. Effects of JNJ-38431055, a novel GPR119 receptor agonist, in randomized, double-blind, placebo-controlled studies in subjects with type 2 diabetes. Diabetes Obes. Metab. 14:709–16 [Google Scholar]
  92. Okawa M, Fujii K, Ohbuchi K, Okumoto M, Aragane K. 92.  et al. 2009. Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion. Biochem. Biophys. Res. Commun. 390:377–81 [Google Scholar]
  93. Shimotoyodome A, Fukuoka D, Suzuki J, Fujii Y, Mizuno T. 93.  et al. 2009. Coingestion of acylglycerols differentially affects glucose-induced insulin secretion via glucose-dependent insulinotropic polypeptide in C57BL/6J mice. Endocrinology 150:2118–26 [Google Scholar]
  94. Chandra R, Wang Y, Shahid RA, Vigna SR, Freedman NJ, Liddle RA. 94.  2013. Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion. J. Clin. Investig. 123:3343–52 [Google Scholar]
  95. Shibue K, Yamane S, Harada N, Hamasaki A, Suzuki K. 95.  et al. 2015. Fatty acid–binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion. Am. J. Physiol. Endocrinol. Metab. 308:E583–91 [Google Scholar]
  96. Poreba MA, Dong CX, Li SK, Stahl A, Miner JH, Brubaker PL. 96.  2012. Role of fatty acid transport protein 4 in oleic acid–induced glucagon-like peptide-1 secretion from murine intestinal L cells. Am. J. Physiol. Endocrinol. Metab. 303:E899–907 [Google Scholar]
  97. Parker HE, Wallis K, le Roux CW, Wong KY, Reimann F, Gribble FM. 97.  2012. Molecular mechanisms underlying bile acid–stimulated glucagon-like peptide-1 secretion. Br. J. Pharmacol. 165:414–23 [Google Scholar]
  98. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J. 98.  et al. 2009. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 10:167–77 [Google Scholar]
  99. Li T, Holmstrom SR, Kir S, Umetani M, Schmidt DR. 99.  et al. 2011. The G protein–coupled bile acid receptor, TGR5, stimulates gallbladder filling. Mol. Endocrinol. 25:1066–71 [Google Scholar]
  100. Brighton CA, Rievaj J, Kuhre RE, Glass LL, Schoonjans K. 100.  et al. 2015. Bile acids trigger GLP-1 release predominantly by accessing basolaterally located G protein-coupled bile acid receptors. Endocrinology 1563961–70
  101. Reimann F, Williams L. Xavier G, Rutter GA, Gribble FM. 101. , da Silva 2004. Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia 47:1592–601 [Google Scholar]
  102. Diakogiannaki E, Pais R, Tolhurst G, Parker HE, Horscroft J. 102.  et al. 2013. Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor. Diabetologia 56:2688–96 [Google Scholar]
  103. Liou AP, Sei Y, Zhao X, Feng J, Lu X. 103.  et al. 2011. The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to l-phenylalanine in acutely isolated intestinal I cells. Am. J. Physiol. Gastrointest. Liver Physiol. 300:G538–46 [Google Scholar]
  104. Mace OJ, Schindler M, Patel S. 104.  2012. The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CaSR in rat small intestine. J. Physiol. 590:2917–36 [Google Scholar]
  105. Nakamura E, Hasumura M, Uneyama H, Torii K. 105.  2011. Luminal amino acid–sensing cells in gastric mucosa. Digestion 83:Suppl. 113–18 [Google Scholar]
  106. Oya M, Kitaguchi T, Pais R, Reimann F, Gribble F, Tsuboi T. 106.  2013. The G protein–coupled receptor family C group 6 subtype A (GPRC6A) receptor is involved in amino acid–induced glucagon-like peptide-1 secretion from GLUTag cells. J. Biol. Chem. 288:4513–21 [Google Scholar]
  107. Haid D, Widmayer P, Breer H. 107.  2011. Nutrient sensing receptors in gastric endocrine cells. J. Mol. Histol. 42:355–64 [Google Scholar]
  108. Wang JH, Inoue T, Higashiyama M, Guth PH, Engel E. 108.  et al. 2011. Umami receptor activation increases duodenal bicarbonate secretion via glucagon-like peptide-2 release in rats. J. Pharmacol. Exp. Ther. 339:464–73 [Google Scholar]
  109. Choi S, Lee M, Shiu AL, Yo SJ, Halldén G, Aponte GW. 109.  2007. GPR93 activation by protein hydrolysate induces CCK transcription and secretion in STC-1 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G1366–75 [Google Scholar]
  110. Miyasaka K, Funakoshi A. 110.  1998. Luminal feedback regulation, monitor peptide, CCK-releasing peptide, and CCK receptors. Pancreas 16:277–83 [Google Scholar]
  111. Friedlander RS, Moss CE, Mace J, Parker HE, Tolhurst G. 111.  et al. 2011. Role of phosphodiesterase and adenylate cyclase isozymes in murine colonic glucagon-like peptide 1 secreting cells. Br. J. Pharmacol. 163:261–71 [Google Scholar]
  112. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. 112.  2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–31 [Google Scholar]
  113. Bogunovic M, Davé SH, Tilstra JS, Chang DT, Harpaz N. 113.  et al. 2007. Enteroendocrine cells express functional Toll-like receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G1770–83 [Google Scholar]
  114. Nguyen AT, Mandard S, Dray C, Deckert V, Valet P. 114.  et al. 2014. Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: involvement of the GLP-1 pathway. Diabetes 63:471–82 [Google Scholar]
  115. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM. 115.  et al. 2012. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61:364–71 [Google Scholar]
  116. Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA. 116.  et al. 2015. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 39:424–29 [Google Scholar]
  117. Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM, Reimann F. 117.  2014. Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Rep. 9:1202–8 [Google Scholar]
  118. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F. 118.  et al. 2008. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein–coupled receptor, Gpr41. PNAS 105:16767–72 [Google Scholar]
  119. Tang C, Ahmed K, Gille A, Lu S, Gröne HJ. 119.  et al. 2015. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat. Med. 21:173–77 [Google Scholar]
  120. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F. 120.  et al. 2009. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–86 [Google Scholar]
  121. Nøhr MK, Egerod KL, Christiansen SH, Gille A, Offermanns S. 121.  et al. 2015. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience 290:126–37 [Google Scholar]
  122. Reimann F, Tolhurst G, Gribble FM. 122.  2012. G-protein-coupled receptors in intestinal chemosensation. Cell Metab. 15:421–31 [Google Scholar]
  123. Gagnon J, Baggio LL, Drucker DJ, Brubaker PL. 123.  2015. Ghrelin is a novel regulator of GLP-1 secretion. Diabetes 64:1513–21 [Google Scholar]
  124. Emery EC, Diakogiannaki E, Gentry C, Psichas A, Habib AM. 124.  et al. 2015. Stimulation of glucagon-like peptide-1 secretion downstream of the ligand-gated ion channel TRPA1. Diabetes 64:1202–10 [Google Scholar]
  125. Cho HJ, Callaghan B, Bron R, Bravo DM, Furness JB. 125.  2014. Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine. Cell Tissue Res. 356:77–82 [Google Scholar]
  126. Bornstein JC. 126.  2012. Serotonin in the gut: What does it do?. Front. Neurosci. 6:16 [Google Scholar]
  127. Li Z, Chalazonitis A, Huang YY, Mann JJ, Margolis KG. 127.  et al. 2011. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J. Neurosci. 31:8998–9009 [Google Scholar]
  128. Pedersen J, Pedersen NB, Brix SW, Grunddal KV, Rosenkilde MM. 128.  et al. 2015. The glucagon-like peptide 2 receptor is expressed in enteric neurons and not in the epithelium of the intestine. Peptides 67:20–28 [Google Scholar]
  129. Richards P, Parker HE, Adriaenssens AE, Hodgson JM, Cork SC. 129.  et al. 2014. Identification and characterization of GLP-1 receptor–expressing cells using a new transgenic mouse model. Diabetes 63:1224–33 [Google Scholar]
  130. De Marinis YZ, Salehi A, Ward CE, Zhang Q, Abdulkader F. 130.  et al. 2010. GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel–dependent exocytosis. Cell Metab. 11:543–53 [Google Scholar]
  131. de Heer J, Rasmussen C, Coy DH, Holst JJ. 131.  2008. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas. Diabetologia 51:2263–70 [Google Scholar]
  132. Drucker DJ, Nauck MA. 132.  2006. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–705 [Google Scholar]
  133. Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. 133.  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. Investig. 91:301–7 [Google Scholar]
  134. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K. 134.  et al. 2002. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat. Med. 8:738–42 [Google Scholar]
  135. Piteau S, Olver A, Kim SJ, Winter K, Pospisilik JA. 135.  et al. 2007. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat. Biochem. Biophys. Res. Commun. 362:1007–12 [Google Scholar]
  136. Finan B, Ma T, Ottaway N, Müller TD, Habegger KM. 136.  et al. 2013. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci. Transl. Med. 5:209ra151 [Google Scholar]
  137. Dockray GJ. 137.  2009. Cholecystokinin and gut-brain signalling. Regul. Pept. 155:6–10 [Google Scholar]
  138. Hisadome K, Reimann F, Gribble FM, Trapp S. 138.  2011. CCK stimulation of GLP-1 neurons involves α1-adrenoceptor-mediated increase in glutamatergic synaptic inputs. Diabetes 60:2701–9 [Google Scholar]
  139. Pocai A, Carrington PE, Adams JR, Wright M, Eiermann G. 139.  et al. 2009. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes 58:2258–66 [Google Scholar]
  140. Karra E, Batterham RL. 140.  2010. The role of gut hormones in the regulation of body weight and energy homeostasis. Mol. Cell. Endocrinol. 316:120–28 [Google Scholar]
  141. Tan T, Bloom S. 141.  2013. Gut hormones as therapeutic agents in treatment of diabetes and obesity. Curr. Opin. Pharmacol. 13:996–1001 [Google Scholar]
  142. Jørgensen NB, Dirksen C, Bojsen-Møller KN, Jacobsen SH, Worm D. 142.  et al. 2013. Exaggerated glucagon-like peptide 1 response is important for improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes 62:3044–52 [Google Scholar]
  143. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. 143.  2011. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54:2506–14 [Google Scholar]
  144. Rubino F, Marescaux J. 144.  2004. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann. Surg. 239:1–11 [Google Scholar]
  145. Alfa RW, Park S, Skelly KR, Poffenberger G, Jain N. 145.  et al. 2015. Suppression of insulin production and secretion by a decretin hormone. Cell Metab. 21:323–33 [Google Scholar]
  146. Kaczmarek P, Malendowicz LK, Pruszynska-Oszmalek E, Wojciechowicz T, Szczepankiewicz D. 146.  et al. 2006. Neuromedin U receptor 1 expression in the rat endocrine pancreas and evidence suggesting neuromedin U suppressive effect on insulin secretion from isolated rat pancreatic islets. Int. J. Mol. Med. 18:951–55 [Google Scholar]
  147. Martinez VG, O'Driscoll L. 147.  2015. Neuromedin U: a multifunctional neuropeptide with pleiotropic roles. Clin. Chem. 61:471–82 [Google Scholar]
  148. Page AJ, Slattery JA, Milte C, Laker R, O'Donnell T. 148.  et al. 2007. Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G1376–84 [Google Scholar]
  149. Skibicka KP, Dickson SL. 149.  2013. Enteroendocrine hormones—central effects on behavior. Curr. Opin. Pharmacol. 13:977–82 [Google Scholar]
  150. Burnicka-Turek O, Mohamed BA, Shirneshan K, Thanasupawat T, Hombach-Klonisch S. 150.  et al. 2012. INSL5-deficient mice display an alteration in glucose homeostasis and an impaired fertility. Endocrinology 153:4655–65 [Google Scholar]
  151. Luo X, Li T, Zhu Y, Dai Y, Zhao J. 151.  et al. 2015. The insulinotrophic effect of insulin-like peptide 5 in vitro and in vivo. Biochem. J. 466:467–73 [Google Scholar]
/content/journals/10.1146/annurev-physiol-021115-105439
Loading
/content/journals/10.1146/annurev-physiol-021115-105439
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error