Skip to main content
SpringerLink
Log in

Gut Peptides

  • Chapter
Book cover Treatment of the Obese Patient

Part of the book series: Contemporary Endocrinology ((COE))

  • 857 Accesses

Abstract

Obesity occurs as a result of excessive energy intake and /or reduced energy expenditure. The hypothalamus is the principal region in the central nervous system that regulates appetite and energy homeostasis by incorporating neural and hormonal signals from the periphery. A large number of such hormones (gut peptides) are synthesized and secreted by cells in the gastrointestinal tract in addition to its function as a digestive system. Increasing evidence supports the role of gut peptides as short-term satiety signals regulating appetite and food intake. The anorexigenic gut peptides include PYY, PP, oxyntomodulin (OXM), GLP-1, and CCK. They are secreted mainly from the intestine, inhibit appetite, and promote satiety, whereas ghrelin, the only orexigenic peptide produced by the stomach, increases food intake. In this chapter we discuss the pathophysiology of gut peptides in health and disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barsh GS, Farooqi IS, O’Rahilly S. Genetics of body-weight regulation. Nature 2000;4046778:644–651.

    PubMed  CAS  Google Scholar 

  2. Butler AA, Cone RD. Knockout studies defining different roles for melanocortin receptors in energy homeostasis. Ann NY Acad Sci 2003;994:240–245.

    PubMed  CAS  Google Scholar 

  3. Butler AA, Kesterson RA, Khong K, et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 2000;141(9):3518–3521.

    Article  PubMed  CAS  Google Scholar 

  4. Butler AA, Cone RD. The melanocortin receptors: lessons from knockout models. Neuropeptides 2002;36(2–3):77–84.

    Article  PubMed  CAS  Google Scholar 

  5. Farooqi IS, Yeo GS, Keogh JM, et al. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest 2000; 106(2):271–279.

    PubMed  CAS  Google Scholar 

  6. Farooqi IS, O’Rahilly S. Monogenic obesity in humans. Annu Rev Med 2005;56:443–458.

    Article  PubMed  CAS  Google Scholar 

  7. Larhammar D. Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regul Pept 1996;65(3): 165–174.

    Article  PubMed  CAS  Google Scholar 

  8. Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002;418(6898):650–654.

    Article  PubMed  CAS  Google Scholar 

  9. Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann NY Acad Sci 2003; 994:162–168.

    PubMed  CAS  Google Scholar 

  10. Broberger C, Landry M, Wong IT, Walsh JN, Hokfelt T. Subtypes Yl and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin-and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus. Neuroendocrinology 1997;66(6):393–408.

    PubMed  CAS  Google Scholar 

  11. Sahu A. Interactions of neuropeptide Y, hypocretin-I (orexin A) and melanin-concentrating hormone on feeding in rats. Brain Res 2002;944(l-2):232–238.

    Article  PubMed  CAS  Google Scholar 

  12. Tatemoto K. Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion. Proc Nat! Acad Sci USA 1982;79(8):2514–2518.

    Article  PubMed  CAS  Google Scholar 

  13. Adrian TE, Ferri GL, Bacarese-Hamilton AJ, et al. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985;89(5): 1070–1077.

    PubMed  CAS  Google Scholar 

  14. Ekblad E, Sundler F. Distribution of pancreaticpolypeptideandpeptideYY. Peptides 2002;23(2):251–261.

    Article  PubMed  CAS  Google Scholar 

  15. Eberlein GA, Eysselein VE, Schaeffer M, et al. A new molecular form of PYY: structural characterization of human PYY(3-36) and PYY(l-36). Peptides 1989; 10(4):797–803.

    Article  PubMed  CAS  Google Scholar 

  16. Pedersen-Bjergaard U, Host U, Kelbaek H, et al. Influence of meal composition on postprandial peripheral plasma concentrations of vasoacti ve peptides in man. Scand J Clin Lab Invest 1996;56(6): 497–503.

    PubMed  CAS  Google Scholar 

  17. Small CJ, Bloom SR. Gut hormones as peripheral anti obesity targets. Curr Drug Targets CNS Neurol Disord 2004;3(5):379–388.

    Article  PubMed  CAS  Google Scholar 

  18. Lin HC, Chey WY. Cholecystokinin and peptide YY are released by fat in either proximal or distal small intestine in dogs. Regul Pept 2003; 114(2–3): 131–135.

    Article  PubMed  CAS  Google Scholar 

  19. Abbott CR, Monteiro M, Small CI, et al. The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstemhypothalamic pathway. Brain Res 2005;1044(l): 127–131.

    Article  PubMed  CAS  Google Scholar 

  20. Koda S, Date Y, Murakami N, et al. The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 2005; 146:2369–2375.

    Article  PubMed  CAS  Google Scholar 

  21. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide Y Y3-36. N Engl J Med 2003;349(10):941–948.

    Article  PubMed  CAS  Google Scholar 

  22. Naslund E, Bogefors J, Skogar S, et al. GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. Am J Physiol 1999;277 (3 Pt 2):R910–R916.

    PubMed  CAS  Google Scholar 

  23. Challis BG, Pionock SB, Coll AP, et al. Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Commun 2003;311(4): 915–919.

    Article  PubMed  CAS  Google Scholar 

  24. Halatchev IG, Ellacott KL, Fan W, et al. Peptide YY3-36 inhibits food intake in mice through a melanocortin-4 receptor-independent mechanism. Endocrinology 2004;145(6):2585–2590.

    Article  PubMed  CAS  Google Scholar 

  25. Chelikani PK, Haver AC, Reidelberger RD. Intravenous infusion of peptide YY (3-36) potently inhibits food intake in rats. Endocrinology 2005; 146(2):879–888.

    Article  PubMed  CAS  Google Scholar 

  26. Abbott CR, Small CJ, Kennedy AR, et al. Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3-36) on food intake. Brain Res 2005;1043(l-2):139–144.

    Article  PubMed  CAS  Google Scholar 

  27. Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann NY Acad Sci 2003; 994:162–168.

    PubMed  CAS  Google Scholar 

  28. Scott V, Kimura N, Stark JA, et al. Intravenous peptide YY3-36 and Y2 receptor antagonism in the rat: effects on feeding behavior. J Neuroendocrinol 2005;17(7):452–457.

    Article  PubMed  CAS  Google Scholar 

  29. Le Roux CW, Bloom SR. Peptide YY, appetite and food intake. Proc Nutr Soc 2005;64(2):213–216.

    Article  PubMed  CAS  Google Scholar 

  30. Kanatani A, Mashiko S, Murai N et al. Role of the Yl receptor in the regulation of neuropeptide Y-mediated feeding: comparison of wild-type, Yl receptor-deficient, and Y5 receptor-deficient mice. Endocrinology 2000;141(3):1011–1016.

    Article  PubMed  CAS  Google Scholar 

  31. Cox JE, Randich A. Enhancement of feeding suppression by PYY(3-36) in rats with area postrema ablations. Peptides 2004;25(6):985–989.

    Article  PubMed  CAS  Google Scholar 

  32. Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann NY Acad Sci 2003; 994:162–168.

    Article  PubMed  CAS  Google Scholar 

  33. Harnisch-Enserer U, Roden M. News in gut-brain communication: a role of peptide YY (PYY) in human obesity and following bariatric surgery? Eur J Clin Invest 2005;35(7):425–430.

    Article  Google Scholar 

  34. McGowan BM, Bloom SR. Peptide YY and appetite control. Curr Opin Pharmacol 2004;4(6):583–588.

    Article  PubMed  CAS  Google Scholar 

  35. Tschop M, Castaneda TR, Joost HG, et al. Physiology: does gut hormone PYY3-36 decrease food intake in rodents? Nature 2004; 430(6996): 1.

    PubMed  Google Scholar 

  36. Moran TH, Smedh U, Kinzig KP, et al. Peptide YY(3-36) inhibits gastric emptying and produces acute reductions in food intake in rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 2005;288(2): R384–R388.

    PubMed  CAS  Google Scholar 

  37. Pittner RA, Moore CX, Bhavsar SP, et al. Effects of PYY[3-36] in rodent models of diabetes and obesity. Int J Obes Relat Metab Disord 2004;28(8):963–971.

    Article  PubMed  CAS  Google Scholar 

  38. Dhillo WS, Bloom SR. Gastrointestinal hormones and regulation of food intake. Horm Metab Res 2004;36(11-12):846–851.

    Article  PubMed  CAS  Google Scholar 

  39. Monteleone P, Martiadis V, Rigamonti AE, et al. Investigation of peptide YY and ghrelin responses to a test meal in bulimia nervosa. Biol Psychiatry 2005;57(8):926–931.

    Article  PubMed  CAS  Google Scholar 

  40. Inamura M. Effects of surgical manipulation of the intestine on peptide YY and its physiology. Peptides 2002;23(2):403–407.

    Article  Google Scholar 

  41. Naslund E, Gryback P, Hellstrom PM, et al. Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass for massive obesity. Int J Obes Relat Metab Disord 1997;21(5):387–392.

    Article  PubMed  CAS  Google Scholar 

  42. Adrian TE, Savage AP, Fuessl HS, et al. Release of peptide YY (PYY) after resection of small bowel, colon, or pancreas in man. Surgery 1987;101(6):715–719.

    PubMed  CAS  Google Scholar 

  43. Wahab PJ, Hopman WP, Jansen JB. Basal and fat-stimulated plasma peptide YY levels in celiac disease. Dig Dis Sci 2001;46(11):2504–2509.

    Article  PubMed  CAS  Google Scholar 

  44. Adrian TE, Savage AP, Bacarese-Hamilton AJ, et al. Peptide Y Y abnormalities in gastrointestinal diseases. Gastroenterology 1986;90(2):379–384.

    PubMed  CAS  Google Scholar 

  45. Le Roux CW, Ghatei VIA, Gibbs JS, Bloom SR. The putative satiety hormone PYY is raised in cardiac cachexia associated with primary pulmonary hypertension. Heart 2005;91(2):241–242.

    Article  PubMed  CAS  Google Scholar 

  46. Mitch WE. Cachexia in chronic kidney disease: a link to defective central nervous system control of appetite. J Clin Invest 2005;115(6): 1476–1478.

    Article  PubMed  CAS  Google Scholar 

  47. Larsson LI, Sundler F, Hakanson R. Immunohistochemical localization of human pancreatic polypeptide (HPP) to a population of islet cells. Cell Tissue Res 1975;156(2): 167–171.

    Article  PubMed  CAS  Google Scholar 

  48. Ueno N, Inui A, Iwamoto M, et al. Decreased food intake and body weight in pancreatic polypeptideoverexpressing mice. Gastroenterology 1999;117(6): 1427–1432.

    Article  PubMed  CAS  Google Scholar 

  49. McLaughlin CL, Baile CA. Obese mice and the satiety effects of cholecystokinin, bombesin and pancreatic polypeptide. Physiol Behav 1981;26(3):433–437.

    Article  PubMed  CAS  Google Scholar 

  50. Track NS, McLeod RS, Mee AV. Human pancreatic polypeptide: studies of fasting and postprandial plasma concentrations. Can J Physiol Pharmacol 1980;58(12): 1484–1489.

    PubMed  CAS  Google Scholar 

  51. Mochiki E, Inui A, Satoh M, et al. Motilin is a biosignal controlling cyclic release of pancreatic polypeptide via the vagus in fasted dogs. Am J Physiol 1997;272 (2 Pt 1):G224–G232.

    PubMed  CAS  Google Scholar 

  52. Peracchi M, Tagliabue R, Quatrini M, Reschini E. Plasma pancreatic polypeptide response to secretin. Eur J Endocrinol 1999;141(l):47–49.

    Article  PubMed  CAS  Google Scholar 

  53. Arosio M, Ronchi CL, Gebbia C, et al. Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. J Clin Endocrinol Metab 2003;88(2):701–704.

    Article  PubMed  CAS  Google Scholar 

  54. Parkinson C, Drake WM, Roberts ME, et al. A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal. J Clin Endocrinol Metab 2002;87(4): 1797–1804.

    Article  PubMed  CAS  Google Scholar 

  55. Uhe AM, Szmukler GI, Collier GR, et al. Potential regulators of feeding behavior in anorexia nervosa. Am J Clin Nutr 1992;55(l):28–32.

    PubMed  CAS  Google Scholar 

  56. Fujimoto S, Inui A, Kiyota N, et al. Increased cholecystokinin and pancreatic polypeptide responses to a fat-rich meal in patients with restrictive but not bulimic anorexia nervosa. Biol Psychiatry 1997;41(10): 1068–1070.

    Article  PubMed  CAS  Google Scholar 

  57. Asakawa A, Inui A, Yuzuriha H, et al. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 2003; 124(5): 1325–1336.

    Article  PubMed  CAS  Google Scholar 

  58. Batterham RL, Le Roux CW, Cohen MA, et al. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 2003;88(8):3989–3992.

    Article  PubMed  CAS  Google Scholar 

  59. Berntson GG, Zipf WB, O’Dorisio TM, et al. Pancreatic polypeptide infusions reduce food intake in Prader-Willi syndrome. Peptides 1993;14(3):497–503.

    Article  PubMed  CAS  Google Scholar 

  60. Liddle RA. Cholecystokinin: its role in health and disease. Curr Opin Endocrinol Diabetes 2003; 10(1): 50–54.

    Article  CAS  Google Scholar 

  61. Moran TH. Gut peptides in the control of food intake: 30 years of ideas. Physiol Behav 2004;82(l): 175–180.

    PubMed  CAS  Google Scholar 

  62. Rehfeld JF. Clinical endocrinology and metabolism. Cholecystokinin. Best Pract Res Clin Endocrinol Metab 2004; 18(4):569–586.

    Article  PubMed  CAS  Google Scholar 

  63. Wank SA, Pisegna JR, de Weerth A. Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc Natl Acad Sci USA 1992;89(18):8691–8695.

    Article  PubMed  CAS  Google Scholar 

  64. Wank SA. Cholecystokinin receptors. Am J Physiol 1995;269 (5 Pt 1):G628–G646.

    PubMed  CAS  Google Scholar 

  65. Beglinger C, Degen L. Fat in the intestine as a regulator of appetite—role of CCK. Physiol Behav 2004;83(4):617–621.

    Article  PubMed  CAS  Google Scholar 

  66. Kissileff HR, Carretta JC, Geliebter A, et al. Cholecystokinin and stomach distension combine to reduce food intake in humans. Am J Physiol Regul Integr Comp Physiol 2003;285(5):R992–R998.

    PubMed  CAS  Google Scholar 

  67. Moran TH, Kinzig KP. Gastrointestinal satiety si gnals II. Cholecystokinin. Am J Physiol Gastrointest Liver Physiol 2004;286(2):G183–G188.

    Article  PubMed  CAS  Google Scholar 

  68. Zittel TT, Glatzle J, Kreis ME, et al. C-fos protein expression in the nucleus of the solitary tract correlates with cholecystokinin dose injected and food intake in rats. Brain Res 1999;846(1): 1–11.

    Article  PubMed  CAS  Google Scholar 

  69. Schwartz GJ, Whitney A, Skoglund C, et al. Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors. Am J Physiol 1999;277 (4 Pt 2):R1144–R1151.

    PubMed  CAS  Google Scholar 

  70. Moran TH, Katz LF, Plata-Salaman CR, Schwartz GJ. Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol 1998;274 (3 Pt 2):R618–R625.

    PubMed  CAS  Google Scholar 

  71. Ghatei MA, Uttenthal LO, Christofides ND, et al. Molecular forms of human enteroglucagon in tissue and plasma: plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract. J Clin Endocrinol Metab 1983;57(3):488–495.

    Article  PubMed  CAS  Google Scholar 

  72. Le Quellec A, Kervran A, Blache P, et al. Oxyntomodulin-like immunoreactivity: diurnal profile of a new potential enterogastrone. J Clin Endocrinol Metab 1992;74(6): 1405–1409.

    Article  PubMed  Google Scholar 

  73. Dakin CL, Gunn I, Small CJ, et al. Oxyntomodulin inhibits food intake in the rat. Endocrinology 2001; 142(10): 4244–4250.

    Article  PubMed  CAS  Google Scholar 

  74. Dakin CL, Small CJ, Batterham RL, et al. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 2004; 145(6):2687–2695.

    Article  PubMed  CAS  Google Scholar 

  75. Dakin CL, Small CJ, Park AJ, et al. Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats. Am J Physiol Endocrinol Metab 2002;283(6): E1173–E1177.

    PubMed  CAS  Google Scholar 

  76. Cohen MA, Ellis SM, Le Roux CW, et al. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab 2003;88(10):4696–4701.

    Article  PubMed  CAS  Google Scholar 

  77. Wynne K, Park AJ, Small CJ, et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes 2005;54(8):2390–2395.

    Article  PubMed  CAS  Google Scholar 

  78. Baggio LL, Huang Q, Brown TJ, et al. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 2004;127(2):546–558.

    Article  PubMed  CAS  Google Scholar 

  79. Fehmann HC, Jiang J, Schweinfurth J, et al. Stable expression of the rat GLP-I receptor in CHO cells: activation and binding characteristics utilizing GLP-I(7-36)-amide, oxyntomodulin, exendin-4, and exendin(9-39). Peptides 1994; 15(3):453–456.

    Article  PubMed  CAS  Google Scholar 

  80. Hoist JJ. Glucagonlike peptide 1: a newly discovered gastrointestinal hormone. Gastroenterology 1994;107(6): 1848–1855.

    Google Scholar 

  81. Drucker DJ, Lovshin J, Baggio L, et al. New developments in the biology of the glucagon-like peptides GLP-1 and GLP-2. Ann NY Acad Sci 2000;921:226–232.

    Article  PubMed  CAS  Google Scholar 

  82. Drucker DJ. Minireview: the glucagon-like peptides. Endocrinology 2001;142(2):521–527.

    Article  PubMed  CAS  Google Scholar 

  83. Tang-Christensen M, Vrang N, Larsen P.I. Glucagon-like peptide containing pathways in the regulation of feeding behavior. Int J Obes Relat Metab Disord 2001;25Suppl 5:S42–S47.

    Article  PubMed  CAS  Google Scholar 

  84. Meeran K, O’Shea D, Edwards CM, et al. Repeated intracerebroventricular administration of glucagon-like peptide-l-(7-36) amide or exendin-(9-39) alters body weight in the rat. Endocrinology 1999;140(l):244–250.

    Article  Google Scholar 

  85. Verdich C, Flint A, Gutzwiller JP, et al. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 2001;86(9):4382–4389.

    Article  PubMed  CAS  Google Scholar 

  86. Verdich C, Toubro S, Buemann B, et al. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction. Int J Obes Relat Metab Disord 2001;25(8): 1206–1214.

    Article  PubMed  CAS  Google Scholar 

  87. Flint A, Raben A, Ersboll AK, et al. The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int J Obes Relat Metab Disord 2001;25(6):781–792.

    Article  PubMed  CAS  Google Scholar 

  88. Gutzwiller JP, Goke B, Drewe J, et al. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 1999;44(l):81–86.

    Article  PubMed  CAS  Google Scholar 

  89. Gutzwiller JP, Drewe J, Goke B, et al. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physio! 1999;276 (5 Pt 2):R1541–R1544.

    CAS  Google Scholar 

  90. Naslund E, Barkeling B, King N, et al. Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 1999;23(3):304–311.

    Article  PubMed  CAS  Google Scholar 

  91. Willms B, Werner J, Hoist JJ, et al. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-l)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 1996;81(l):327–332.

    Article  PubMed  CAS  Google Scholar 

  92. MacDonald PE, El Kholy W, Riedel MJ, et al. The multiple actions of GLP-1 on the process of glucosestimulated insulin secretion. Diabetes 2002;51Suppl 3:S434–S442.

    Article  PubMed  CAS  Google Scholar 

  93. Wishart JM, Horowitz M, Morris HA, et al. Relation between gastric emptying of glucose and plasma concentrations of glucagon-like peptide-1. Peptides 1998;19(6): 1049–1053.

    Article  PubMed  CAS  Google Scholar 

  94. Zander M, Madsbad S, Madsen JL, et al. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359(9309):824–830.

    Article  PubMed  CAS  Google Scholar 

  95. Egan JM, Bulotta A, Hui H, et al. GLP-1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells. Diabetes Metab Res Rev 2003; 19(2): 115–123.

    Article  PubMed  CAS  Google Scholar 

  96. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402(6762):656–660.

    Article  PubMed  CAS  Google Scholar 

  97. Ariyasu H, Takaya K, Tagami T, et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001;86(10):4753–4758.

    Article  PubMed  CAS  Google Scholar 

  98. Kojima S, Nakahara T, Nagai N, et al. Altered ghrelin and peptide Y Y responses to meals in bulimia nervosa. Clin Endocrinol (Oxf) 2005;62(l):74–78.

    Article  CAS  Google Scholar 

  99. Cowley MA, Smith RG, Diano S, et al. The distribution and mechani sm of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 2003;37(4):649–661.

    Article  PubMed  CAS  Google Scholar 

  100. Cummings DE, Foster-Schubert KE, Overduin J. Ghrelin and energy balance: focus on current controversies. Curr Drug Targets 2005;6(2): 153–169.

    PubMed  CAS  Google Scholar 

  101. Asakawa A, Inui A, Kaga T, et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 2001;120(2):337–345.

    Article  PubMed  CAS  Google Scholar 

  102. Cummings DE, Purnell JQ, Frayo RS, et al. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50(8): 1714–1719.

    Article  PubMed  CAS  Google Scholar 

  103. Kojima M, Kangawa K. Ghrelin: structure and function. Physio! Rev 2005;85(2):495–522.

    Article  CAS  Google Scholar 

  104. Williams DL, Cummings DE. Regulation of ghrelin in physiologic and pathophysiologic states. J Nutr 2005; 135(5): 1320–1325.

    PubMed  CAS  Google Scholar 

  105. Shiiya T, Nakazato M, Mizuta M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002;87(l):240–244.

    Article  PubMed  CAS  Google Scholar 

  106. Le Roux CW, Patterson M, Vincent RP, et al. Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects. J Clin Endocrinol Metab 2005;90(2):1068–1071.

    Article  PubMed  CAS  Google Scholar 

  107. Murdolo G, Lucidi P, Di Loreto C et al. Insulin is required for prandial ghrelin suppression in humans. Diabetes 2003;52(12):2923–2927.

    Article  PubMed  CAS  Google Scholar 

  108. Masuda Y, Tanaka T, Inomata N, et al. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 2000;276(3):905–908.

    Article  PubMed  CAS  Google Scholar 

  109. Date Y, Kojima M, Hosoda H, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000; 141(11): 4255–4261.

    Article  PubMed  CAS  Google Scholar 

  110. Tang-Christensen M, Vrang N, Ortmann S, et al. Central administration of ghrelin and agouti-related protein (83-132) increases food intake and decreases spontaneous locomotor activity in rats. Endocrinology 2004;145(10):4645–4652.

    Article  PubMed  CAS  Google Scholar 

  111. Wren AM, Small CJ, Fribbens CV, et al. The hypothalamic mechanisms of the hypophysiotropic action of ghrelin. Neuroendocrinology 2002;76(5):316–324.

    Article  PubMed  CAS  Google Scholar 

  112. Wren AM, Small CJ, Abbott CR, et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes 2001;50(ll):2540–2547.

    Article  PubMed  CAS  Google Scholar 

  113. Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001;86(12):5992.

    Article  PubMed  CAS  Google Scholar 

  114. Shintani M, Ogawa Y, Ebihara K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001;50(2):227–232.

    Article  PubMed  CAS  Google Scholar 

  115. Hewson AK, Dickson SL. Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats. J Neuroendocrinol 2000;12(l1): 1047–1049.

    Article  PubMed  CAS  Google Scholar 

  116. Toshinai K, Date Y, Murakami N, et al. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 2003; 144(4): 1506–1512

    Article  PubMed  CAS  Google Scholar 

  117. Le Roux CW, Neary NM, Halsey TJ, et al. Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab 2005;90(8):4521–4524.

    Article  PubMed  CAS  Google Scholar 

  118. Le Roux CW, Patterson M, Vincent RP, et al. Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects. J Clin Endocrinol Metab 2005;90(2): 1068–1071.

    Article  PubMed  CAS  Google Scholar 

  119. Shiiya T, Nakazato M, Mizut M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002;87(l):240–244.

    Article  PubMed  CAS  Google Scholar 

  120. Tschop M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50(4):707–709.

    Article  PubMed  CAS  Google Scholar 

  121. Nagaya N, Uematsu VI, Kojima M, et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001;104(17):2034–2038.

    Article  PubMed  CAS  Google Scholar 

  122. Otto B, Cuntz U, Fruehauf E, et al. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 2001;145(5):669–673.

    PubMed  CAS  Google Scholar 

  123. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346(21): 1623–1630.

    Article  PubMed  Google Scholar 

  124. Talsania T, Anini Y, Siu S, et al. Peripheral exendin-4 and peptide YY3-36 synergistically reduce food intake through different mechanisms in mice. Endocrinology 2005;146(9):3748–3756.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

    Vian Amber MBChB, MSc, PhD, MRCPath

  2. Department of Metabolic Medicine, Imperial College London, Hammersmith Campus, London, UK

    Stephen R. Bloom MBChB, MA, FRCP, FRCPath, DSc, MD

Authors
  1. Vian Amber MBChB, MSc, PhD, MRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen R. Bloom MBChB, MA, FRCP, FRCPath, DSc, MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL

    Robert F. Kushner MD

  2. Division of Endocrinology, University of Colorado at Denver and Health Sciences Center, Denver, CO

    Daniel H. Bessesen MD

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Amber, V., Bloom, S.R. (2007). Gut Peptides. In: Kushner, R.F., Bessesen, D.H. (eds) Treatment of the Obese Patient. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-400-1_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-400-1_2

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-735-8

  • Online ISBN: 978-1-59745-400-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation