Skip to main content
SpringerLink
Log in

Using the body’s natural signals — gut hormones

  • Chapter
Pharmacotherapy of Obesity

Part of the book series: Milestones in Drug Therapy ((MDT))

  • 776 Accesses

Abstract

The balance between energy (food) intake and energy expenditure is closely regulated to keep body weight stable over time. Increasingly, however, the homeostatic mechanisms responsible are failing to keep pace with societal changes in eating behaviour and activity levels. The prevalence of obesity in many parts of the world has now reached epidemic proportions. It is estimated that it causes 30,000 deaths per year in the UK, and in the USA it is set to overtake smoking as the leading cause of preventable illness and premature death [1, 2]. Current strategies for the non-surgical treatment of the morbidly obese have met with limited success [3–5] and without the development of more effective treatments, the socioeconomic and public health implications of an unchecked rise in obesity are grave.

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 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
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. National Audit Office (2001) Tackling obesity in England: a report by the Comptroller and Auditor General.

    Google Scholar 

  2. Mokdad AH, Mark JS, Stroup DF, Gerberding JL (2004) Actual causes of death in the United States, 2000. JAMA 291: 1238–1245

    Article  PubMed  Google Scholar 

  3. Kaplan LM (2005) Pharmacological therapies for obesity. Gastroenterol Clin North Am 34: 91–104

    Article  PubMed  Google Scholar 

  4. Thearle M, Aronne LJ (2003) Obesity and pharmacologic therapy. Endocrinol Metab Clin North Am 32: 1005–1024

    Article  PubMed  CAS  Google Scholar 

  5. Yanovski SZ, Yanovski JA (2002) Obesity. N Engl J Med 346: 591–602

    Article  PubMed  CAS  Google Scholar 

  6. Stanley S, Wynne K, McGowan B, Bloom S (2005) Hormonal regulation of food intake. Physiol Rev 85: 1131–1158

    Article  PubMed  CAS  Google Scholar 

  7. Wynne K, Stanley S, McGowan B, Bloom S (2005) Appetite control. J Endocrinol 184: 291–318

    Article  PubMed  CAS  Google Scholar 

  8. Dockray GJ (1979) Comparative biochemistry and physiology of gut hormones. Annu Rev Physiol 41: 83–95

    Article  PubMed  CAS  Google Scholar 

  9. Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB (2004) Ghrelin — a hormone with multiple functions. Front Neuroendocrinol 25: 27–68

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Dockray GJ (2004) Clinical endocrinology and metabolism. Gastrin. Best Pract Res Clin Endocrinol Metab 18: 555–568

    Article  PubMed  CAS  Google Scholar 

  12. Geloneze B, Tambascia MA, Pilla VF, Geloneze SR, Repetto EM, Pareja JC (2003) Ghrelin: a gut-brain hormone: effect of gastric bypass surgery. Obes Surg 13: 17–22

    Article  PubMed  Google Scholar 

  13. Korner J, Bessler M, Cirilo LJ, Conwell IM, Daud A, Restuccia NL, Wardlaw SL (2005) Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab 90: 359–365

    Article  PubMed  CAS  Google Scholar 

  14. Service GJ, Thompson GB, Service FJ, Andrews JC, Collazo-Clavell ML, Lloyd RV (2005) Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med 353: 249–254

    Article  PubMed  CAS  Google Scholar 

  15. Cone RD, Cowley MA, Butler AA, Fan W, Marks DL, Low MJ (2001) The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord 25Suppl 5: S63–S67

    PubMed  CAS  Google Scholar 

  16. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404: 661–671

    PubMed  CAS  Google Scholar 

  17. Gibbs J, Young RC, Smith GP (1973) Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 84: 488–495

    Article  PubMed  CAS  Google Scholar 

  18. Kissileff HR, Pi-Sunyer FX, Thornton J, Smith GP (1981) C-terminal octapeptide of cholecys-tokinin decreases food intake in man. Am J Clin Nutr 34: 154–160

    PubMed  CAS  Google Scholar 

  19. McLaughlin CL, Baile CA, Buonom FC (1985) Effect of CCK antibodies on food intake and weight gain in Zucker rats. Physiol Behav 34: 277–282

    Article  PubMed  CAS  Google Scholar 

  20. Meereis-Schwanke K, Klonowski-Stumpe H, Herberg L, Niederau C (1998) Long-term effects of CCK-agonist and-antagonist on food intake and body weight in Zucker lean and obese rats. Peptides 19: 291–299

    Article  PubMed  CAS  Google Scholar 

  21. Moran TH, Katz LF, Plata-Salaman CR, Schwartz GJ (1998) Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol 214: R618–R625

    Google Scholar 

  22. West DB, Fey D, Woods SC (1984) Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 246: R776–R787

    PubMed  CAS  Google Scholar 

  23. West DB, Greenwood MR, Sullivan AC, Prescod L, Marzullo LR, Triscari J (1987) Infusion of cholecystokinin between meals into free-feeding rats fails to prolong the intermeal interval. Physiol Behav 39: 111–115

    Article  PubMed  CAS  Google Scholar 

  24. Crawley JN, Beinfeld MC (1983) Rapid development of tolerance to the behavioural actions of cholecystokinin. Nature 302: 703–706

    Article  PubMed  CAS  Google Scholar 

  25. Fuhlendorff J, Johansen NL, Melberg SG, Thogersen H, Schwartz TW (1990) The antiparallel pancreatic polypeptide fold in the binding of neuropeptide Y to Y1 and Y2 receptors. J Biol Chem 265: 11706–11712

    PubMed  CAS  Google Scholar 

  26. Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, Quirion R, Schwartz T, Westfall T (1998) XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev 50: 143–150

    PubMed  CAS  Google Scholar 

  27. Adrian TE, Bloom SR, Bryant MG, Polak JM, Heitz PH, Barnes AJ (1976) Distribution and release of human pancreatic polypeptide. Gut 17: 940–944

    Article  PubMed  CAS  Google Scholar 

  28. Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, Frost GS, Ghatei MA, Bloom SR (2003) Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 88: 3989–3992

    Article  PubMed  CAS  Google Scholar 

  29. Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G, Fujimiya M, Fujino MA, Niijima A, Meguid MM, Kasuga M (2003) Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 124: 1325–1336

    Article  PubMed  CAS  Google Scholar 

  30. Asakawa A, Inui A, Ueno N, Fujimiya M, Fujino MA, Kasuga M (1999) Mouse pancreatic polypeptide modulates food intake, while not influencing anxiety in mice. Peptides 20: 1445–1448

    Article  PubMed  CAS  Google Scholar 

  31. Zipf WB, O’Dorisio TM, Cataland S, Sotos J (1981) Blunted pancreatic polypeptide responses in children with obesity of Prader-Willi syndrome. J Clin Endocrinol Metab 52: 1264–1266

    Article  PubMed  CAS  Google Scholar 

  32. Fujimoto S, Inui A, Kiyota N, Seki W, Koide K, Takamiya S, Uemoto M, Nakajima Y, Baba S, Kasuga M (1997) Increased cholecystokinin and pancreatic polypeptide responses to a fat-rich meal in patients with restrictive but not bulimic anorexia nervosa. Biol Psychiatry 41: 1068–1070

    Article  PubMed  CAS  Google Scholar 

  33. Malaisse-Lagae F, Carpentier JL, Patel YC, Malaisse WJ, Orci L (1977) Pancreatic polypeptide: a possible role in the regulation of food intake in the mouse. Hypothesis. Experientia 33: 915–917

    Article  PubMed  CAS  Google Scholar 

  34. Ueno N, Inui A, Iwamoto M, Kaga T, Asakawa A, Okita M, Fujimiya M, Nakajima Y, Ohmoto Y, Ohnaka M et al. (1999) Decreased food intake and body weight in pancreatic polypeptide-over-expressing mice. Gastroenterology 117: 1427–1432

    Article  PubMed  CAS  Google Scholar 

  35. Campbell RE, Smith MS, Allen SE, Grayson BE, Ffrench-Mullen JM, Grove KL (2003) Orexin neurons express a functional pancreatic polypeptide Y4 receptor. J Neurosci 23: 1487–1497

    PubMed  CAS  Google Scholar 

  36. Jorde R, Burhol PG (1984) Fasting and postprandial plasma pancreatic polypeptide (PP) levels in obesity. Int J Obes 8: 393–397

    PubMed  CAS  Google Scholar 

  37. Wisen O, Bjorvell H, Cantor P, Johansson C, Theodorsson E (1992) Plasma concentrations of regulatory peptides in obesity following modified sham feeding (MSF) and a liquid test meal. Regul Pept 39: 43–54

    Article  PubMed  CAS  Google Scholar 

  38. Schmidt PT, Naslund E, Gryback P, Jacobsson H, Holst JJ, Hilsted L, Hellstrom PM (2005) A role for pancreatic polypeptide in the regulation of gastric emptying and short term metabolic control. J Clin Endocrinol Metab 90: 5241–5246

    Article  PubMed  CAS  Google Scholar 

  39. Berntson GG, Zipf WB, O’Dorisio TM, Hoffman JA, Chance RE (1993) Pancreatic polypeptide infusions reduce food intake in Prader-Willi syndrome. Peptides 14: 497–503

    Article  PubMed  CAS  Google Scholar 

  40. Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR (1985) Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89: 1070–1077

    PubMed  CAS  Google Scholar 

  41. Hagan MM (2002) Peptide YY: a key mediator of orexigenic behavior. Peptides 23: 377–382

    Article  PubMed  CAS  Google Scholar 

  42. Kanatani A, Mashiko S, Murai N, Sugimoto N, Ito J, Fukuroda T, Fukami T, Morin N, MacNeil DJ, Van der Ploeg LH et al. (2000) Role of the Y1 receptor in the regulation of neuropeptide Y-mediated feeding: comparison of wild-type, Y1 receptor-deficient, and Y5 receptor-deficient mice. Endocrinology 141: 1011–1016

    Article  PubMed  CAS  Google Scholar 

  43. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA et al. (2002) Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418: 650–654

    Article  PubMed  CAS  Google Scholar 

  44. Abbott CR, Small CJ, Kennedy AR, Neary NM, Sajedi A, Ghatei MA, Bloom SR (2005) 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 1043: 139–144

    Article  PubMed  CAS  Google Scholar 

  45. Scott V, Kimura N, Stark JA, Luckman SM (2005) Intravenous peptide YY3-36 and Y2 receptor antagonism in the rat: effects on feeding behaviour. J Neuroendocrinol 17: 452–457

    Article  PubMed  CAS  Google Scholar 

  46. Nonaka N, Shioda S, Niehoff ML, Banks WA (2003) Characterization of blood-brain barrier permeability to PYY3-36 in the mouse. J Pharmacol Exp Ther 306: 948–953

    Article  PubMed  CAS  Google Scholar 

  47. Koda S, Date Y, Murakami N, Shimbara T, Hanada T, Toshinai K, Niijima A, Furuya M, Inomata N, Osuye K et al. (2005) The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 146: 2369–2375

    Article  PubMed  CAS  Google Scholar 

  48. Abbott CR, Monteiro M, Small CJ, Sajedi A, Smith KL, Parkinson JR, Ghatei MA, Bloom SR (2005) 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-brainstem-hypothalamic pathway. Brain Res 1044: 127–131

    Article  PubMed  CAS  Google Scholar 

  49. Halatchev IG, Cone RD (2005) Peripheral administration of PYY(3–36) produces conditioned taste aversion in mice. Cell Metab 1: 159–168

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  51. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR (2003) Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 349: 941–948

    Article  PubMed  CAS  Google Scholar 

  52. le Roux CW, Batterham RL, Aylwin SJ, Patterson M, Borg CM, Wynne KJ, Kent A, Vincent RP, Gardiner J, Ghatei MA et al. (2005) Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 147: 3–8

    Article  PubMed  CAS  Google Scholar 

  53. Boggiano MM, Chandler PC, Oswald KD, Rodgers RJ, Blundell JE, Ishii Y, Beattie AH, Holch P, Allison DB, Schindler M et al. (2005) PYY3-36 as an anti-obesity drug target. Obes Rev 6: 307–322

    Article  PubMed  CAS  Google Scholar 

  54. Neary NM, Small CJ, Druce MR, Park AJ, Ellis SM, Semjonous NM, Dakin CL, Filipsson K, Wang F, Kent AS et al. (2005) Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively. Endocrinology 146: 5120–5127

    Article  PubMed  CAS  Google Scholar 

  55. Nordheim U, Hofbauer KG (2004) Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens. Am J Physiol Regul Integr Comp Physiol 286: R138–R142

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  57. Challis BG, Pinnock SB, Coll AP, Carter RN, Dickson SL, O’Rahilly S (2003) Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Commun 311: 915–919

    Article  PubMed  CAS  Google Scholar 

  58. Talsania T, Anini Y, Siu S, Drucker DJ, Brubaker PL (2005) Peripheral exendin-4 and peptide YY3-36 synergistically reduce food intake through different mechanisms in mice. Endocrinology 146: 3748–3756

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  60. Shechter Y, Tsubery H, Mironchik M, Rubinstein M, Fridkin M (2005) Reversible PEGylation of peptide YY3-36 prolongs its inhibition of food intake in mice. FEBS Lett 579: 2439–2444

    Article  PubMed  CAS  Google Scholar 

  61. Riediger T, Bothe C, Becskei C, Lutz TA (2004) Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression. Neuroendocrinology 79: 317–326

    Article  PubMed  CAS  Google Scholar 

  62. Challis BG, Coll AP, Yeo GS, Pinnock SB, Dickson SL, Thresher RR, Dixon J, Zahn D, Rochford JJ, White A et al. (2004) Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3–36). Proc Natl Acad Sci USA 101: 4695–4700

    Article  PubMed  CAS  Google Scholar 

  63. Adams SH, Won WB, Schonhoff SE, Leiter AB, Paterniti JR Jr, (2004) Effects of peptide YY[3–36] on short-term food intake in mice are not affected by prevailing plasma ghrelin levels. Endocrinology 145: 4967–4975

    Article  PubMed  CAS  Google Scholar 

  64. Pittner RA, Moore CX, Bhavsar SP, Gedulin BR, Smith PA, Jodka CM, Parkes DG, Paterniti JR, Srivastava VP, Young AA (2004) Effects of PYY[3–36] in rodent models of diabetes and obesity. Int J Obes Relat Metab Disord 28: 963–971

    Article  PubMed  CAS  Google Scholar 

  65. Martin NM, Small CJ, Sajedi A, Patterson M, Ghatei MA, Bloom SR (2004) Pre-obese and obese agouti mice are sensitive to the anorectic effects of peptide YY(3–36) but resistant to ghrelin. Int J Obes Relat Metab Disord 28: 886–893

    Article  PubMed  CAS  Google Scholar 

  66. Abbott CR, Small CJ, Sajedi A, Smith KL, Parkinson JR, Broadhead LL, Ghatei MA, Bloom SR (2005) The importance of acclimatisation and habituation to experimental conditions when investigating the anorectic effects of gastrointestinal hormones in the rat. Int J Obes (Land) 30: 288–292

    Article  CAS  Google Scholar 

  67. Kas MJ, Bruijnzeel AW, Haanstra JR, Wiegant VM, Adan RA (2005) Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event. J Mol Endocrinol 35: 159–164

    Article  PubMed  CAS  Google Scholar 

  68. Ghamari-Langroudi M, Colmers WF, Cone RD (2005) PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors. Cell Metab 2: 191–199

    Article  PubMed  CAS  Google Scholar 

  69. Acuna-Goycolea C, van den Pol AN (2005) Peptide YY(3–36) inhibits both anorexigenic proopiomelanocortin and orexigenic neuropeptide Y neurons: implications for hypothalamic regulation of energy homeostasis. J Neurosci 25: 10510–10519

    Article  PubMed  CAS  Google Scholar 

  70. Moran TH, Smedh U, Kinzig KP, Scott KA, Knipp S, Ladenheim EE (2004) Peptide YY (3–36) inhibits gastric emptying and produces acute reductions in food intake in rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 288: R384–388

    PubMed  Google Scholar 

  71. Sileno AP, Brandt GC, Spann BM, Quay SC (2005) Lower mean weight after 14 days intravenous administration peptide YY(3–36) (PYY(3–36)) in rabbits. Int J Obes (Lond) 30: 68–72

    Article  CAS  Google Scholar 

  72. Koegler FH, Enriori PJ, Billes SK, Takahashi DL, Martin MS, Clark RL, Evans AE, Grove KL, Cameron L, Cowley MA (2005) Peptide YY(3–36) inhibits morning, but not evening, food intake and decreases body weight in rhesus macaques. Diabetes 54: 3198–3204

    Article  PubMed  CAS  Google Scholar 

  73. Brandt G, Park A, Wynne K, Sileno A, Jazrawi R, Woods A, Quay S, Bloom S (2004) Nasal peptide YY3-36: Phase 1 dose ranging and safety studies in healthy human subjects. 86th Annual Meeting of the Endocrine Society (ENDO 2004), New Orleans, LA

    Google Scholar 

  74. Kieffer TJ, Habener JF (1999) The glucagon-like peptides. Endocr Rev 20: 876–913

    Article  PubMed  CAS  Google Scholar 

  75. Eissele R, Goke R, Willemer S, Harthus HP, Vermeer H, Arnold R, Goke B (1992) Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22: 283–291

    Article  PubMed  CAS  Google Scholar 

  76. Orskov C, Rabenhoj L, Wettergren A, Kofod H, Holst JJ (1994) Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes 43: 535–539

    Article  PubMed  CAS  Google Scholar 

  77. Holst JJ (2005) Glucagon-like peptide-1: physiology and therapeutic potential. Curr Opin Endocrinol Diabetes 12: 56–62

    Article  CAS  Google Scholar 

  78. Wei Y, Mojsov S (1995) Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett 358: 219–224

    Article  PubMed  CAS  Google Scholar 

  79. Shughrue PJ, Lane MV, Merchenthaler I (1996) Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus. Endocrinology 137: 5159–5162

    Article  PubMed  CAS  Google Scholar 

  80. Turton MD, O’Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD et al. (1996) A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379: 69–72

    Article  PubMed  CAS  Google Scholar 

  81. Meeran K, O’Shea D, Edwards CM, Turton MD, Heath MM, Gunn I, Abusnana S, Rossi M, Small CJ, Goldstone AP et al. (1999) Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat. Endocrinology 140: 244–250

    Article  PubMed  CAS  Google Scholar 

  82. Scrocchi LA, Brown TJ, MaClusky N, Brubaker PL, Auerbach AB, Joyner AL, Drucker DJ (1996) Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 2: 1254–1258

    Article  PubMed  CAS  Google Scholar 

  83. Kinzig KP, D’Alessio DA, Seeley RJ (2002) The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness. J Neurosci 22: 10470–10476

    PubMed  CAS  Google Scholar 

  84. Verdich C, Flint A, Gutzwiller JP, Naslund E, Beglinger C, Hellstrom PM, Long SJ, Morgan LM, Holst JJ, Astrup A (2001) 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 86: 4382–4389

    Article  PubMed  CAS  Google Scholar 

  85. Verdich C, Toubro S, Buemann B, Lysgard MJ, Juul HJ, Astrup A (2001) 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 25: 1206–1214

    Article  PubMed  CAS  Google Scholar 

  86. Feinle C, Chapman IM, Wishart J, Horowitz M (2002) Plasma glucagon-like peptide-1 (GLP-1) responses to duodenal fat and glucose infusions in lean and obese men. Peptides 23: 1491–1495

    Article  PubMed  CAS  Google Scholar 

  87. Zander M, Madsbad S, Madsen JL, Holst JJ (2002) 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 359: 824–830

    Article  PubMed  CAS  Google Scholar 

  88. Naslund E, King N, Mansten S, Adner N, Holst JJ, Gutniak M, Hellstrom PM (2004) Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects. Br J Nutr 91: 439–446

    Article  PubMed  CAS  Google Scholar 

  89. Nauck MA, Meier JJ (2005) Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regul Pept 128: 135–148

    Article  PubMed  CAS  Google Scholar 

  90. Purnell JQ, Weyer C (2003) Weight effect of current and experimental drugs for diabetes mellitus: from promotion to alleviation of obesity. Treat Endocrinol 2: 33–47

    Article  PubMed  CAS  Google Scholar 

  91. Larsen PJ, Fledelius C, Knudsen LB, Tang-Christensen M (2001) Systemic administration of the long-acting GLP-1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes 50: 2530–2539

    Article  PubMed  CAS  Google Scholar 

  92. Fineman MS, Shen LZ, Taylor K, Kim DD, Baron AD (2004) Effectiveness of progressive doseescalation of exenatide (exendin-4) in reducing dose-limiting side effects in subjects with type 2 diabetes. Diabetes Metab Res Rev 20: 411–417

    Article  PubMed  CAS  Google Scholar 

  93. Yamamoto H, Kishi T, Lee CE, Choi BJ, Fang H, Hollenberg AN, Drucker DJ, Elmquist JK (2003) Glucagon-like peptide-1-responsive catecholamine neurons in the area postrema link peripheral glucagon-like peptide-1 with central autonomic control sites. J Neurosci 23: 2939–2946

    PubMed  CAS  Google Scholar 

  94. Edwards CM, Edwards AV, Bloom R (1997) Cardiovascular and pancreatic endocrine responses to glucagon-like peptide-1(7–36) amide in the conscious calf. Exp Physiol 82: 709–716

    PubMed  CAS  Google Scholar 

  95. Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, Bloom SR (2001) Oxyntomodulin inhibits food intake in the rat. Endocrinology 142: 4244–4250

    Article  PubMed  CAS  Google Scholar 

  96. Dakin CL, Small CJ, Batterham RL, Neary NM, Cohen MA, Patterson M, Ghatei MA, Bloom SR (2004) Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 145: 2687–2695

    Article  PubMed  CAS  Google Scholar 

  97. Baggio LL, Huang Q, Brown TJ, Drucker DJ (2004) Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 127: 546–558

    Article  PubMed  CAS  Google Scholar 

  98. Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR (2003) Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab 88: 4696–4701

    Article  PubMed  CAS  Google Scholar 

  99. Wynne K, Park AJ, Small CJ, Patterson M, Ellis SM, Murphy KG, Wren AM, Frost GS, Meeran K, Ghatei MA et al. (2005) Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes 54: 2390–2395

    Article  PubMed  CAS  Google Scholar 

  100. Dakin CL, Small CJ, Park AJ, Seth A, Ghatei MA, Bloom SR (2002) Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats. Am J Physiol Endocrinol Metab 283: E1173–E1177

    PubMed  CAS  Google Scholar 

  101. Burkey BF, Li X, Bolognese L, Balkan B, Mone M, Russell M, Hughes TE, Wang PR (2005) Acute and chronic effects of the incretin enhancer vildagliptin in insulin-resistant rats. J Pharmacol Exp Ther 315: 688–695

    Article  PubMed  CAS  Google Scholar 

  102. Sudre B, Broqua P, White RB, Ashworth D, Evans DM, Haigh R, Junien JL, Aubert ML (2002) Chronic inhibition of circulating dipeptidyl peptidase IV by FE 999011 delays the occurrence of diabetes in male zucker diabetic fatty rats. Diabetes 51: 1461–1469

    Article  PubMed  CAS  Google Scholar 

  103. Pospisilik JA, Stafford SG, Demuth HU, McIntosh CH, Pederson RA (2002) Long-term treatment with dipeptidyl peptidase IV inhibitor improves hepatic and peripheral insulin sensitivity in the VDF Zucker rat: a euglycemic-hyperinsulinemic clamp study. Diabetes 51: 2677–2683

    Article  PubMed  CAS  Google Scholar 

  104. Reimer MK, Holst JJ, Ahren B (2002) Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice. Eur J Endocrinol 146: 717–727

    Article  PubMed  CAS  Google Scholar 

  105. Drucker DJ (2001) Glucagon-like peptide 2. J Clin Endocrinol Metab 86: 1759–1764

    Article  PubMed  CAS  Google Scholar 

  106. Ahren B, Gomis R, Standl E, Mills D, Schweizer A (2004) Twelve-and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 27: 2874–2880

    Article  PubMed  CAS  Google Scholar 

  107. Hollander P, Maggs DG, Ruggles JA, Fineman M, Shen L, Kolterman OG, Weyer C (2004) Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obes Res 12: 661–668

    PubMed  CAS  Google Scholar 

  108. Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, Batterham RL, Taheri S, Stanley SA, Ghatei MA et al. (2001) Ghrelin causes hyperphagia and obesity in rats. Diabetes 50: 2540–2547

    Article  PubMed  CAS  Google Scholar 

  109. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86: 5992–5995

    Article  PubMed  CAS  Google Scholar 

  110. Tschop M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407: 908–913

    Article  PubMed  CAS  Google Scholar 

  111. Hansen TK, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen JS, Jorgensen JO (2002) Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf) 56: 203–206

    Article  CAS  Google Scholar 

  112. Neary NM, Small CJ, Wren AM, Lee JL, Druce MR, Palmieri C, Frost GS, Ghatei MA, Coombes RC, Bloom SR (2004) Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 89: 2832–2836

    Article  PubMed  CAS  Google Scholar 

  113. Nagaya N, Itoh T, Murakami S, Oya H, Uematsu M, Miyatake K, Kangawa K (2005) Treatment of cachexia with ghrelin in patients with COPD. Chest 128: 1187–1193

    Article  PubMed  CAS  Google Scholar 

  114. Wynne K, Giannitsopoulou K, Small CJ, Patterson M, Frost G, Ghatei MA, Brown EA, Bloom SR, Choi P (2005) Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritoneal dialysis: a randomized, placebo-controlled trial. J Am Soc Nephrol 16: 2111–2118

    Article  PubMed  CAS  Google Scholar 

  115. Ogihara T, Matsuzaki M, Matsuoka H, Shimamoto K, Shimada K, Rakugi H, Umemoto S, Kamiya A, Suzuki N, Kumagai H et al. (2005) The combination therapy of hypertension to prevent cardiovascular events (COPE) trial: rationale and design. Hypertens Res 28: 331–338

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Metabolic Medicine, Imperial College London, Hammersmith Hospital, London, W12 ONN, UK

    Owais B. Chaudhri, Kirsty L. Smith & Stephen R. Bloom

Authors
  1. Owais B. Chaudhri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kirsty L. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen R. Bloom
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Clinical Sciences Centre, University Hospital Aintree, Longmoor Lane, Liverpool, L9 7AL, UK

    John P. H. Wilding

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Birkhäuser Verlag/Switzerland

About this chapter

Cite this chapter

Chaudhri, O.B., Smith, K.L., Bloom, S.R. (2008). Using the body’s natural signals — gut hormones. In: Wilding, J.P.H. (eds) Pharmacotherapy of Obesity. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7425-9_7

Download citation

Publish with us

Policies and ethics

Search

Navigation