Advertisement

Role of the Gastrointestinal Tract in Peptide Hormone Release and Appetite

  • Joan Khoo
  • Christopher K. Rayner
  • Christine Feinle-Bisset
  • Gary Wittert
Chapter

Abstract

Far from being a passive reservoir for digestion and absorption of food, the gastrointestinal tract is a dynamic participant in the regulation of appetite and energy homeostasis. During meals, distension of the stomach and delivery of the products of carbohydrate, lipid, and protein digestion to the small intestine act synergistically to limit food intake. Satiation is induced by the activation of vagal afferent nerves terminals in gastric and intestinal walls, and the secretion of peptide hormones such as cholecystokinin, leptin, glucagon-like peptide-1, oxyntomodulin, and peptide YY from specialized mucosal cells in the stomach and small intestine. These gut peptides exert their effects by endocrine and paracrine actions, the latter via vagal afferents. The vagus interacts with the enteric nervous system and the central nervous system to coordinate satiation signaling. In addition to inhibiting appetite centers in the hypothalamus and brainstem, gut hormones prolong the exposure of the gastrointestinal tract to nutrients by slowing gastric emptying and intestinal transit. The mechanisms by which nutrients stimulate the release of gut hormones are now known to include activation of mucosal “taste” receptors and G-protein coupled receptors in the small intestine by carbohydrates, proteins, and fatty acids. Pharmacological agonists and antagonists of gut peptides are potentially useful for the management of obesity, type 2 diabetes, gastrointestinal motility disorders, and cachexia of critical illness.

Keywords

Gastric Emptying Pancreatic Polypeptide Reduce Food Intake Gastric Distension Vagal Afferents 
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.

Abbreviations

BBB

Blood–brain barrier

CB1

Cannabinoid-1

CCK

Cholecystokinin

CCK1R

Cholecystokin-1 receptor

CNS

Central nervous system

DPP-4

Dipeptidyl peptidase-4

GLP-1

Glucagon-like peptide-1

LCFA

Long-chain fatty acid

MCH-1

Melanin-concentrating hormone-1

OXM

Oxyntomodulin

PP

Pancreatic polypeptide

PYY

Peptide YY

Notes

Acknowledgements

Christopher K Rayner, Christine Feinle-Bisset and Gary Wittert are in receipt of funding from the National Health and Medical Research Council of Australia.

Glossary

Satiety: 

The suppression of hunger in between meals that reduces the frequency of eating.

Satiation: 

The processes that terminate feeding and limit meal size i.e. the feeling of “fullness” after ingestion of food.

Orexigenic: 

Appetite-stimulating (contrasts with anorexigenic = appetite suppressing)

Enteric nervous system: 

The network of neurons in the gastrointestinal tract (collected into ­submucosal and myenteric nerve plexuses), which control gut motility, secretion, and immune function.

Migrating motor complex(es): 

Waves of activity which pass down the intestines in regular cycles during fasting, and which facilitate transport of nutrients and other substances from proximal to distal parts of the gastrointestinal tract.

Enteroendocrine cells: 

Specialized cells in the gastrointestinal tract (e.g., L cells) that secrete ­hormones such as cholecystokinin, glucagon-like peptide-1, and peptide YY in response to luminal nutrients.

Incretin: 

An endocrine transmitter produced by the gastrointestinal tract which stimulates insulin secretion in response to postprandial hyperglycemia.

Ileal brake: 

Negative feedback mechanisms, by which the transit of nutrients to the ileum stimulates vagal signaling and the release of satiating gut peptides to inhibit gastric, duodenal, and jejunal motility and secretion.

Bariatric surgery: 

Surgical therapy for obesity, to restrict gastric capacity with intestinal malabsorption (e.g., Roux-en-Y gastric bypass) or without it (e.g., laparoscopic adjustable gastric banding).

Gastroparesis: 

A clinical disorder characterized by delayed gastric emptying, in the absence of mechanical obstruction, most frequently presenting with upper gastrointestinal symptoms such as nausea and vomiting.

References

  1. Abbott CR, Monteiro M, Small CJ, Sajedi A, Smith KL, Parkinson JR, Ghatei MA, Bloom SR. Brain Res. 2005;1044:127–31PubMedCrossRefGoogle Scholar
  2. Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G, Fujimiya M, Fujino MA, Niijima A, Meguid MM, Kasuga M. Gastroenterology. 2003;124:1325–36.PubMedCrossRefGoogle Scholar
  3. Banks WA. Regul Pept. 2008;149:11–4PubMedCrossRefGoogle Scholar
  4. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Nature. 2002;418:650–4PubMedCrossRefGoogle Scholar
  5. Batterham RL, le Roux CW, Cohen MA, Park AJ, Ellis SM. J Clin Endocrinol Metab. 2003;88:3989–92PubMedCrossRefGoogle Scholar
  6. Beglinger C, Poller B, Arbit E, Ganzoni C, Gass S, Gomez-Orellana I, Drewe J. Clin Pharm Ther. 2008;84:468–74CrossRefGoogle Scholar
  7. Berthoud HR. Regul Pept. 2008;149:15-25.Google Scholar
  8. Camilleri M. Gastroenterology. 2006;131:640–58.PubMedCrossRefGoogle Scholar
  9. Caminos JE, Bravo SB, García-Rendueles ME, Ruth González C, Garcés MF, Cepeda LA, Lage R, Suárez MA, López M, Diéguez C. Regul Pept. 2008;146:106–11.PubMedCrossRefGoogle Scholar
  10. Cammisotto PG, Bendayan M. Histol Histopathol. 2007;22:199–210.PubMedGoogle Scholar
  11. Cohen MA, Ellis SM, le Roux CW. J Clin Endocrinol Metab. 2003;88:4696–701.PubMedCrossRefGoogle Scholar
  12. Cummings DE, Overduin J. J Clin Invest. 2007;117:13–23.PubMedCrossRefGoogle Scholar
  13. Cumming DE. physiol Behav. 2006;89:71–84Google Scholar
  14. Dakin CL, Small CJ, Batterham RL, Neary NM, Cohen MA. Endocrinology. 2004;145:2687–95.PubMedCrossRefGoogle Scholar
  15. Davidson I, Smith S. Proc Nutr Soc 2007;66:346–50.PubMedCrossRefGoogle Scholar
  16. Degen L, Oesch S, Casanova M, Graf S, Ketterer S, Drewe J, Beglinger C. Gastroenterology. 2005;129:1430–6.PubMedCrossRefGoogle Scholar
  17. Dockray GJ. Regul Pept. 2009;155:6–10.PubMedCrossRefGoogle Scholar
  18. Drucker DJ, Nauck MA. Lancet. 2006;368:1696–705.PubMedCrossRefGoogle Scholar
  19. Feinle C, Grundy D, Read NW. Am J Physiol. 1997;273:G721–6.PubMedGoogle Scholar
  20. Feinle C, O’Donovan DG, Doran S, Andrews JM, Wishart J, Chapman I, Horowitz M. Am J Physiol Gastrointest Liver Physiol. 2003;284:G798–807.PubMedGoogle Scholar
  21. Geary N. Physiol Behav. 2004;81:719–33.PubMedCrossRefGoogle Scholar
  22. Guilmeau S, Buyse M, Bado A. Curr Opin Pharmacol. 2004;4:561–6.PubMedCrossRefGoogle Scholar
  23. Guo Y, Ma L, Enriori PJ, Koska J, Franks PW, Brookshire T, Cowley M, Salbe AD, Delparigi A, Tataranni PA. Obesity (Silver Spring). 2006;14:1562–70.CrossRefGoogle Scholar
  24. Izzo AA, Camilleri M. Gut. 2008;57:1140–55.PubMedCrossRefGoogle Scholar
  25. Kamiji MM, Inui A. Curr Opin Clin Nutr Metab Care. 2008;11:443–51.PubMedCrossRefGoogle Scholar
  26. Karra E, Chandarana K, Batterham RL. J Physiol. 2009;587:19–25.PubMedCrossRefGoogle Scholar
  27. Kissileff HR, Carretta JC, Geliebter A, Pi-Sunyer FX. Am J Physiol Regul Integr Comp Physiol. 2003;285:R992–8.PubMedGoogle Scholar
  28. Kuo P, Chaikomin R, Pilichiewicz A, O’Donovan D, Wishart JM, Meyer JH, Jones KL, Feinle-Bisset C, Horowitz M, Rayner CK. Regul Pept. 2008;146:1–3.PubMedCrossRefGoogle Scholar
  29. Ladabaum U, Koshy SS, Woods ML, Hooper FG, Owyang C, Hasler WL. Am J Physiol. 1998;275:G418–24.PubMedGoogle Scholar
  30. Lam TKT, Gutierrez-Juarez R, Pocai A, Bhanot S, Tso P, Schwartz GJ, Rossetti L. Nat Med. 2007;13:171–80.PubMedCrossRefGoogle Scholar
  31. le Roux CW, Aylwin JBS, Batterham RL, Borg CM, Coyle F, Prasad V, Shurey S, Ghatei MA, Patel AG, Bloom SR. Ann Surg. 2006;243:108–14.PubMedCrossRefGoogle Scholar
  32. Little TJ, Horowitz M, Feinle-Bisset C. Obes Rev. 2005;6:297–306.PubMedCrossRefGoogle Scholar
  33. Little TJ, Doran S, Meyer JH, Smout AJPM, O’Donovan DG, Wu KL, Jones KL, Wishart J, Rayner CK, Horowitz M. Am J Physiol Endocrinol Metab. 2006;291:E647–55.PubMedCrossRefGoogle Scholar
  34. Lauffer LM, Iakoubov R, Brubaker PL. Diabetes. 2009;58:1058–66.PubMedCrossRefGoogle Scholar
  35. Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL, Horowitz M, Rayner CK (2009) Am J Physiol Gastrointest Liver Physiol. 296:G735–739PubMedCrossRefGoogle Scholar
  36. Maida A, Lovshin JA, Baggio LL, Drucker DJ. Endocrinology. 2008;149:5670–8.PubMedCrossRefGoogle Scholar
  37. Maljaars PWJ, Peters HPF, Masclee AAM. Physiol Behav. 2008;95:271–81.PubMedCrossRefGoogle Scholar
  38. Meyer JH, Tabrizi Y, DiMaso N, Hlinka M, Rayboud HE. Am J Physiol. 1998;275:R1308–19.PubMedGoogle Scholar
  39. Mondal MS, Yamaguchi H, Date Y, Shimbara T, Toshinai K, Shimomura Y, Mori M, Nakazato M. Endocrinology. 2003;144:4729–33.PubMedCrossRefGoogle Scholar
  40. Moran TH, Baldessarinin AR, Salorio CF, Lowery T, Schwartz GJ. Am J Physiol. 1997;272:R1245–51.PubMedGoogle Scholar
  41. Morínigo R, Moizé V, Musri M, Lacy AM, Navarro S, Marín JL, Delgado S, Casamitjana R, Vidal J. J Clin Endocrinol Metab. 2006;91:1735–40.PubMedCrossRefGoogle Scholar
  42. Mundinger TO, Cummings DE, Taborsky GJ. Endocrinology. 2006;147:2893–901.PubMedCrossRefGoogle Scholar
  43. O’Donovan D, Feinle-Bisset C, Wishart J, Horowitz M. Br J Nutr. 2003;90:849–52.PubMedCrossRefGoogle Scholar
  44. Obici S, Feng Z, Arduini A, Conti R, Rossetti L. Nature Med. 2003;9:756–61.PubMedCrossRefGoogle Scholar
  45. Pilichiewicz AN, Papadopoulos P, Brennan IM, Little TJ, Meyer JH, Wishart JM, Horowitz M, Feinle-Bisset C. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2170–8.PubMedCrossRefGoogle Scholar
  46. Potier M, Darcel N, Tomé D. Curr Opin Clin Nutr Metab Care. 2009;12:54–8.PubMedCrossRefGoogle Scholar
  47. Read NW, McFarlane A, Kinsman Ri, Bates TE, Blackgall NW, Farrar GB. Gastroenterology. 1984;86:274–80.PubMedGoogle Scholar
  48. Ritter RC. Physiol Behav. 2004;81:249–73.PubMedCrossRefGoogle Scholar
  49. Rozengurt E. Am J Physiol Gastrointest Liver Physiol. 2006;291:G171–7.PubMedCrossRefGoogle Scholar
  50. Seimon RV, Feltrin KL, Meyer JH, Brennan IM, Wishart JM, Horowitz M, Feinle-Bisset C. Am J Physiol Regul Integr Comp Physiol. 2009;296:R912–20.PubMedCrossRefGoogle Scholar
  51. Strader AD, Vahl TP, Jandacek RJ, Woods SC, D’Alessio DA, Seeley RJ. Am J Physiol Endocrinol Metab. 2005;288:E447–53.PubMedCrossRefGoogle Scholar
  52. Sturm K, Parker B, Wishart J, Feinle-Bisset C, Jones KL, Chapman I, Horowitz M. Am J Clin Nutr. 2004;80:656–67.PubMedGoogle Scholar
  53. Vincent RP, le Roux CW. Clin Endocrinol. 2008;69:173–9.CrossRefGoogle Scholar
  54. Wang PYT, Caspi L, Lam CKL, Chari M, Li X, Light PE, Gutierrez-Juarez R, Ang, Schwartz GJ, Lam TKT. Nature. 2008;452:1012–6.Google Scholar
  55. Wargin W, Thomas H, Clohs L, St-Louis C, Ejskjaer N, Gutierrez M, Shaughnessy L, Kosutic G. Clin Drug Invest. 2009;29:409–18.CrossRefGoogle Scholar
  56. Williams DL, Baskin DG, Schwartz MW. Endocrinology. 2009;150:1680–7.PubMedCrossRefGoogle Scholar
  57. Young RL, Sutherland K, Pezos N, Brierley SM, Horowitz M, Rayner CK, Blackshaw LA. Gut. 2009;58:337–46.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Joan Khoo
    • 1
  • Christopher K. Rayner
  • Christine Feinle-Bisset
  • Gary Wittert
  1. 1.Discipline of MedicineRoyal Adelaide HospitalAdelaideAustralia

Personalised recommendations