Skip to main content
SpringerLink
Log in

GI Peptides, Energy Balance, and Cancer

  • Chapter
  • First Online:
Adipocytokines, Energy Balance, and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 12))

  • 541 Accesses

Abstract

Beyond its role in nutrient absorption, the gastrointestinal tract is a vital endocrine organ responsible for the production of a variety of regulatory peptides that modulate energy balance. In this chapter, the most studied gastrointestinal peptides are described, with emphasis on their roles played in appetite control, glucose homeostasis, and weight disorders. Translational research investigating drug development targeting the “gut–brain” axis regulatory pathway for the treatment of obesity and diabetes is also highlighted. Several GI peptides have proliferative and/or pro-apoptotic functions and their possible cancer-related effects are discussed.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

References

  1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N et al (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384:766–781

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ligibel JA, Alfano CM, Courneya KS, Demark-Wahnefried W, Burger RA et al (2014) American Society of Clinical Oncology position statement on obesity and cancer. J Clin Oncol 32:3568–3574

    Article  PubMed  PubMed Central  Google Scholar 

  3. O'Neill S, O'Driscoll L (2015) Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev 16:1–12

    Article  PubMed  Google Scholar 

  4. Shin JA, Lee JH, Lim SY, Ha HS, Kwon HS et al (2013) Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness. J Diabetes Investig 4:334–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Vincent RP, Ashrafian H, le Roux CW (2008) Mechanisms of disease: the role of gastrointestinal hormones in appetite and obesity. Nat Clin Pract Gastroenterol Hepatol 5:268–277

    Article  CAS  PubMed  Google Scholar 

  6. Gibbs J, Young RC, Smith GP (1973) Cholecystokinin elicits satiety in rats with open gastric fistulas. Nature 245:323–325

    Article  CAS  PubMed  Google Scholar 

  7. Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP et al (2012) Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 366:1567–1576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W et al (2004) Bariatric surgery: a systematic review and meta-analysis. JAMA 292:1724–1737

    Article  CAS  PubMed  Google Scholar 

  9. Ionut V, Burch M, Youdim A, Bergman RN (2013) Gastrointestinal hormones and bariatric surgery-induced weight loss. Obesity 21:1093–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Doucet E (2008) Gastrointestinal peptides after bariatric surgery and appetite control: are they in tuning? Curr Opin Clin Nutr Metab Care 11:645–650

    Article  CAS  PubMed  Google Scholar 

  11. Neff KJ, O'Shea D, le Roux CW (2013) Glucagon like peptide-1 (GLP-1) dynamics following bariatric surgery: a signpost to a new frontier. Curr Diabetes Rev 9:93–101

    CAS  PubMed  Google Scholar 

  12. Korner J, Inabnet W, Febres G, Conwell IM, McMahon DJ et al (2009) Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes 33:786–795

    Article  CAS  Google Scholar 

  13. Laferrere B (2009) Effect of gastric bypass surgery on the incretins. Diabetes Metabol 35:513–517

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. Kojima M, Hosoda H, Matsuo H, Kangawa K (2001) Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab 12:118–122

    Article  CAS  PubMed  Google Scholar 

  16. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA et al (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273:974–977

    Article  CAS  PubMed  Google Scholar 

  17. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS et al (2000) 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 141:4255–4261

    CAS  PubMed  Google Scholar 

  18. Dornonville de la Cour C, Bjorkqvist M, Sandvik AK, Bakke I, Zhao CM et al (2001) A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control. Regul Pept 99:141–150

    Article  CAS  PubMed  Google Scholar 

  19. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS et al (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992

    Article  CAS  PubMed  Google Scholar 

  20. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P et al (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87:2988

    Article  CAS  PubMed  Google Scholar 

  21. Broglio F, Benso A, Gottero C, Prodam F, Gauna C et al (2003) Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans. J Endocrinol Investig 26:192–196

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Trudel L, Tomasetto C, Rio MC, Bouin M, Plourde V et al (2002) Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat. Am J Physiol Gastrointest Liver Physiol 282:G948–G952

    Article  CAS  PubMed  Google Scholar 

  24. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H et al (2001) A role for ghrelin in the central regulation of feeding. Nature 409:194–198

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Hosoda H, Kojima M, Kangawa K (2002) Ghrelin and the regulation of food intake and energy balance. Mol Interv 2:494–503

    Article  CAS  PubMed  Google Scholar 

  27. Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR et al (2004) Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 145:2607–2612

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  29. Callahan HS, Cummings DE, Pepe MS, Breen PA, Matthys CC et al (2004) Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans. J Clin Endocrinol Metab 89:1319–1324

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  31. Shimizu Y, Nagaya N, Isobe T, Imazu M, Okumura H et al (2003) Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res 9:774–778

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. Borg CM, le Roux CW, Ghatei MA, Bloom SR, Patel AG et al (2006) Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety. Br J Surg 93:210–215

    Article  CAS  PubMed  Google Scholar 

  36. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE et al (2002) Elevated plasma ghrelin levels in Prader–Willi syndrome. Nat Med 8:643–644

    Article  CAS  PubMed  Google Scholar 

  37. Bizzarri C, Rigamonti AE, Luce A, Cappa M, Cella SG et al (2010) Children with Prader–Willi syndrome exhibit more evident meal-induced responses in plasma ghrelin and peptide YY levels than obese and lean children. Eur J Endocrinol 162:499–505

    Article  CAS  PubMed  Google Scholar 

  38. Banks WA, Tschop M, Robinson SM, Heiman ML (2002) Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 302:822–827

    Article  CAS  PubMed  Google Scholar 

  39. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A et al (2002) The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 123:1120–1128

    Article  CAS  PubMed  Google Scholar 

  40. Cowley MA, Smith RG, Diano S, Tschop M, Pronchuk N et al (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37:649–661

    Article  CAS  PubMed  Google Scholar 

  41. le Roux CW, Neary NM, Halsey TJ, Small CJ, Martinez-Isla AM et al (2005) Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab 90:4521–4524

    Article  PubMed  CAS  Google Scholar 

  42. Yada T, Dezaki K, Sone H, Koizumi M, Damdindorj B et al (2008) Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential. Curr Diabetes Rev 4:18–23

    Article  CAS  PubMed  Google Scholar 

  43. Tong J, Prigeon RL, Davis HW, Bidlingmaier M, Kahn SE et al (2010) Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes 59:2145–2151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Poykko SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA et al (2003) Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 52:2546–2553

    Article  PubMed  Google Scholar 

  45. Barazzoni R, Zanetti M, Ferreira C, Vinci P, Pirulli A et al (2007) Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome. J Clin Endocrinol Metab 92:3935–3940

    Article  CAS  PubMed  Google Scholar 

  46. Goldstone AP, Thomas EL, Brynes AE, Castroman G, Edwards R et al (2004) Elevated fasting plasma ghrelin in Prader–Willi syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance. J Clin Endocrinol Metab 89:1718–1726

    Article  CAS  PubMed  Google Scholar 

  47. Kojima M, Kangawa K (2005) Ghrelin: structure and function. Physiol Rev 85:495–522

    Article  CAS  PubMed  Google Scholar 

  48. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL (2008) Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132:387–396

    Article  CAS  PubMed  Google Scholar 

  49. Gualillo O, Lago F, Dieguez C (2008) Introducing GOAT: a target for obesity and anti-diabetic drugs? Trends Pharmacol Sci 29:398–401

    Article  CAS  PubMed  Google Scholar 

  50. Yang J, Zhao TJ, Goldstein JL, Brown MS (2008) Inhibition of ghrelin O-acyltransferase (GOAT) by octanoylated pentapeptides. Proc Natl Acad Sci U S A 105:10750–10755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Barnett BP, Hwang Y, Taylor MS, Kirchner H, Pfluger PT et al (2010) Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor. Science 330:1689–1692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chan CB, Kashemsant N (2006) Regulation of insulin secretion by uncoupling protein. Biochem Soc Trans 34:802–805

    Article  CAS  PubMed  Google Scholar 

  53. An JY, Choi MG, Noh JH, Sohn TS, Jin DK et al (2007) Clinical significance of ghrelin concentration of plasma and tumor tissue in patients with gastric cancer. J Surg Res 143:344–349

    Article  CAS  PubMed  Google Scholar 

  54. Ekeblad S, Nilsson B, Lejonklou MH, Johansson T, Stalberg P et al (2006) Gastrointestinal stromal tumors express the orexigen ghrelin. Endocr Relat Cancer 13:963–970

    Article  CAS  PubMed  Google Scholar 

  55. Papotti M, Cassoni P, Volante M, Deghenghi R, Muccioli G et al (2001) Ghrelin-producing endocrine tumors of the stomach and intestine. J Clin Endocrinol Metab 86:5052–5059

    Article  CAS  PubMed  Google Scholar 

  56. Waseem T, Javaid Ur R, Ahmad F, Azam M, Qureshi MA (2008) Role of ghrelin axis in colorectal cancer: a novel association. Peptides 29:1369–1376

    Article  CAS  PubMed  Google Scholar 

  57. Cassoni P, Papotti M, Ghe C, Catapano F, Sapino A et al (2001) Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab 86:1738–1745

    CAS  PubMed  Google Scholar 

  58. Jeffery PL, Murray RE, Yeh AH, McNamara JF, Duncan RP et al (2005) Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocr Relat Cancer 12:839–850

    Article  CAS  PubMed  Google Scholar 

  59. Cassoni P, Allia E, Marrocco T, Ghe C, Ghigo E et al (2006) Ghrelin and cortistatin in lung cancer: expression of peptides and related receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line. J Endocrinol Investig 29:781–790

    Article  CAS  Google Scholar 

  60. Fung JN, Seim I, Wang D, Obermair A, Chopin LK et al (2010) Expression and in vitro functions of the ghrelin axis in endometrial cancer. Hormones Cancer 1:245–255

    Article  CAS  PubMed  Google Scholar 

  61. Yeh AH, Jeffery PL, Duncan RP, Herington AC, Chopin LK (2005) Ghrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer. Clin Cancer Res 11:8295–8303

    Article  CAS  PubMed  Google Scholar 

  62. Gaytan F, Morales C, Barreiro ML, Jeffery P, Chopin LK et al (2005) Expression of growth hormone secretagogue receptor type 1a, the functional ghrelin receptor, in human ovarian surface epithelium, mullerian duct derivatives, and ovarian tumors. J Clin Endocrinol Metab 90:1798–1804

    Article  CAS  PubMed  Google Scholar 

  63. Gurgul E, Kasprzak A, Blaszczyk A, Biczysko M, Surdyk-Zasada J et al (2015) Ghrelin and obestatin in thyroid gland – immunohistochemical expression in nodular goiter, papillary and medullary cancer. Folia Histochem Cytobiol 53:19–25

    Article  CAS  PubMed  Google Scholar 

  64. Chen JH, Huang SM, Chen CC, Tsai CF, Yeh WL et al (2011) Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-kappaB signaling pathway in glioma cells. J Cell Biochem 112:2931–2941

    Article  CAS  PubMed  Google Scholar 

  65. Chopin L, Walpole C, Seim I, Cunningham P, Murray R et al (2011) Ghrelin and cancer. Mol Cell Endocrinol 340:65–69

    Article  CAS  PubMed  Google Scholar 

  66. Granata R, Settanni F, Biancone L, Trovato L, Nano R et al (2007) Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3',5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology 148:512–529

    Article  CAS  PubMed  Google Scholar 

  67. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S et al (2002) Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 159:1029–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kim MS, Yoon CY, Jang PG, Park YJ, Shin CS et al (2004) The mitogenic and antiapoptotic actions of ghrelin in 3T3-L1 adipocytes. Mol Endocrinol 18:2291–2301

    Article  CAS  PubMed  Google Scholar 

  69. Chung H, Kim E, Lee DH, Seo S, Ju S et al (2007) Ghrelin inhibits apoptosis in hypothalamic neuronal cells during oxygen-glucose deprivation. Endocrinology 148:148–159

    Article  CAS  PubMed  Google Scholar 

  70. Yang M, Hu S, Wu B, Miao Y, Pan H et al (2007) Ghrelin inhibits apoptosis signal-regulating kinase 1 activity via upregulating heat-shock protein 70. Biochem Biophys Res Commun 359:373–378

    Article  CAS  PubMed  Google Scholar 

  71. Bonfili L, Cuccioloni M, Cecarini V, Mozzicafreddo M, Palermo FA et al (2013) Ghrelin induces apoptosis in colon adenocarcinoma cells via proteasome inhibition and autophagy induction. Apoptosis 18:1188–1200

    Article  CAS  PubMed  Google Scholar 

  72. Xu Y, Pang X, Dong M, Wen F, Zhang Y (2013) Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro. Oncol Rep 30:2063–2070

    CAS  PubMed  Google Scholar 

  73. Duxbury MS, Waseem T, Ito H, Robinson MK, Zinner MJ et al (2003) Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. Biochem Biophys Res Commun 309:464–468

    Article  CAS  PubMed  Google Scholar 

  74. Tian C, Zhang L, Hu D, Ji J (2013) Ghrelin induces gastric cancer cell proliferation, migration, and invasion through GHS-R/NF-kappaB signaling pathway. Mol Cell Biochem 382:163–172

    Article  CAS  PubMed  Google Scholar 

  75. Fujitsuka N, Asakawa A, Uezono Y, Minami K, Yamaguchi T et al (2011) Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival. Transl Psychiatry 1:e23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hanada T, Toshinai K, Date Y, Kajimura N, Tsukada T et al (2004) Upregulation of ghrelin expression in cachectic nude mice bearing human melanoma cells. Metab Clin Exp 53:84–88

    Article  CAS  PubMed  Google Scholar 

  77. Wang W, Andersson M, Iresjo BM, Lonnroth C, Lundholm K (2006) Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia. Int J Oncol 28:1393–1400

    CAS  PubMed  Google Scholar 

  78. Moore B (1906) On the treatment of Diabetus mellitus by acid extract of Duodenal Mucous Membrane. Biochem J 1:28–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Drucker DJ (2006) The biology of incretin hormones. Cell Metab 3:153–165

    Article  CAS  PubMed  Google Scholar 

  80. Drucker DJ (2003) Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 26:2929–2940

    Article  CAS  PubMed  Google Scholar 

  81. Yip RG, Boylan MO, Kieffer TJ, Wolfe MM (1998) Functional GIP receptors are present on adipocytes. Endocrinology 139:4004–4007

    Article  CAS  PubMed  Google Scholar 

  82. Krarup T, Holst JJ, Larsen KL (1985) Responses and molecular heterogeneity of IR-GIP after intraduodenal glucose and fat. Am J Phys 249:E195–E200

    CAS  Google Scholar 

  83. Falko JM, Crockett SE, Cataland S, Mazzaferri EL (1975) Gastric inhibitory polypeptide (GIP) stimulated by fat ingestion in man. J Clin Endocrinol Metab 41:260–265

    Article  CAS  PubMed  Google Scholar 

  84. Tseng CC, Jarboe LA, Wolfe MM (1994) Regulation of glucose-dependent insulinotropic peptide gene expression by a glucose meal. Am J Phys 266:G887–G891

    CAS  Google Scholar 

  85. Carr RD, Larsen MO, Winzell MS, Jelic K, Lindgren O et al (2008) Incretin and islet hormonal responses to fat and protein ingestion in healthy men. Am J Physiol Endocrinol Metab 295:E779–E784

    Article  CAS  PubMed  Google Scholar 

  86. Wolfe MM, Zhao KB, Glazier KD, Jarboe LA, Tseng CC (2000) Regulation of glucose-dependent insulinotropic polypeptide release by protein in the rat. Am J Physiol Gastrointest Liver Physiol 279:G561–G566

    CAS  PubMed  Google Scholar 

  87. Higashimoto Y, Opara EC, Liddle RA (1995) Dietary regulation of glucose-dependent insulinotropic peptide (GIP) gene expression in rat small intestine. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 110:207–214

    Article  CAS  PubMed  Google Scholar 

  88. Besterman HS, Cook GC, Sarson DL, Christofides ND, Bryant MG et al (1979) Gut hormones in tropical malabsorption. Br Med J 2:1252–1255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Usdin TB, Mezey E, Button DC, Brownstein MJ, Bonner TI (1993) Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain. Endocrinology 133:2861–2870

    CAS  PubMed  Google Scholar 

  90. Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2157

    Article  CAS  PubMed  Google Scholar 

  91. Mentlein R, Gallwitz B, Schmidt WE (1993) Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 214:829–835

    Article  CAS  PubMed  Google Scholar 

  92. Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF et al (2004) Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 53:654–662

    Article  CAS  PubMed  Google Scholar 

  93. Pederson RA, Brown JC (1972) Inhibition of histamine-, pentagastrin-, and insulin-stimulated canine gastric secretion by pure “gastric inhibitory polypeptide”. Gastroenterology 62:393–400

    CAS  PubMed  Google Scholar 

  94. Dupre J, Ross SA, Watson D, Brown JC (1973) Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab 37:826–828

    Article  CAS  PubMed  Google Scholar 

  95. Szecowka J, Grill V, Sandberg E, Efendic S (1982) Effect of GIP on the secretion of insulin and somatostatin and the accumulation of cyclic AMP in vitro in the rat. Acta Endocrinol 99:416–421

    CAS  PubMed  Google Scholar 

  96. Ding WG, Gromada J (1997) Protein kinase A-dependent stimulation of exocytosis in mouse pancreatic beta-cells by glucose-dependent insulinotropic polypeptide. Diabetes 46:615–621

    Article  CAS  PubMed  Google Scholar 

  97. Kang G, Chepurny OG, Holz GG (2001) cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic beta-cells. J Physiol 536:375–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Shibasaki T, Takahashi H, Miki T, Sunaga Y, Matsumura K et al (2007) Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP. Proc Natl Acad Sci U S A 104:19333–19338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tseng CC, Zhang XY, Wolfe MM (1999) Effect of GIP and GLP-1 antagonists on insulin release in the rat. Am J Phys 276:E1049–E1054

    CAS  Google Scholar 

  100. Gault VA, Irwin N, Green BD, McCluskey JT, Greer B et al (2005) Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. Diabetes 54:2436–2446

    Article  CAS  PubMed  Google Scholar 

  101. McClean PL, Irwin N, Cassidy RS, Holst JJ, Gault VA et al (2007) GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. Am J Physiol Endocrinol Metab 293:E1746–E1755

    Article  CAS  PubMed  Google Scholar 

  102. Jones IR, Owens DR, Luzio SD, Hayes TM (1989) Obesity is associated with increased post-prandial GIP levels which are not reduced by dietary restriction and weight loss. Diabete Metab 15:11–22

    CAS  PubMed  Google Scholar 

  103. Crockett SE, Mazzaferri EL, Cataland S (1976) Gastric inhibitory polypeptide (GIP) in maturity-onset diabetes mellitus. Diabetes 25:931–935

    Article  CAS  PubMed  Google Scholar 

  104. Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ (2001) Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50:609–613

    Article  CAS  PubMed  Google Scholar 

  105. Vollmer K, Holst JJ, Baller B, Ellrichmann M, Nauck MA et al (2008) Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 57:678–687

    Article  CAS  PubMed  Google Scholar 

  106. Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R et al (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 Invest 91:301–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Meier JJ, Hucking K, Holst JJ, Deacon CF, Schmiegel WH et al (2001) Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes 50:2497–2504

    Article  CAS  PubMed  Google Scholar 

  108. Song DH, Wolfe MM (2007) Glucose-dependent insulinotropic polypeptide and its role in obesity. Curr Opin Endocrinol Diabetes Obesity 14:46–51

    Article  CAS  Google Scholar 

  109. Klein S, Mittendorfer B, Eagon JC, Patterson B, Grant L et al (2006) Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology 130:1564–1572

    Article  CAS  PubMed  Google Scholar 

  110. Clements RH, Gonzalez QH, Long CI, Wittert G, Laws HL (2004) Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg 70:1–4, discussion 4-5

    PubMed  Google Scholar 

  111. Guidone C, Manco M, Valera-Mora E, Iaconelli A, Gniuli D et al (2006) Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes 55:2025–2031

    Article  CAS  PubMed  Google Scholar 

  112. Rubino F, Gagner M, Gentileschi P, Kini S, Fukuyama S et al (2004) The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg 240:236–242

    Article  PubMed  PubMed Central  Google Scholar 

  113. Miras AD, le Roux CW (2013) Mechanisms underlying weight loss after bariatric surgery. Nat Rev Gastroenterol Hepatol 10:575–584

    Article  PubMed  Google Scholar 

  114. Beck B, Max JP (1987) Hypersensitivity of adipose tissue to gastric inhibitory polypeptide action in the obese Zucker rat. Cell Mol Biol 33:555–562

    CAS  PubMed  Google Scholar 

  115. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K et al (2002) Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 8:738–742

    Article  CAS  PubMed  Google Scholar 

  116. Waser B, Rehmann R, Sanchez C, Fourmy D, Reubi JC (2012) Glucose-dependent insulinotropic polypeptide receptors in most gastroenteropancreatic and bronchial neuroendocrine tumors. J Clin Endocrinol Metab 97:482–488

    Article  CAS  PubMed  Google Scholar 

  117. Gourni E, Waser B, Clerc P, Fourmy D, Reubi JC et al (2014) The glucose-dependent insulinotropic polypeptide receptor: a novel target for neuroendocrine tumor imaging-first preclinical studies. J Nucl Med 55:976–982

    Article  CAS  PubMed  Google Scholar 

  118. Prabakaran D, Wang B, Feuerstein JD, Sinclair JA, Bijpuria P et al (2010) Glucose-dependent insulinotropic polypeptide stimulates the proliferation of colorectal cancer cells. Regul Pept 163:74–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bell GI, Santerre RF, Mullenbach GT (1983) Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature 302:716–718

    Article  CAS  PubMed  Google Scholar 

  120. Orskov C, Holst JJ, Knuhtsen S, Baldissera FG, Poulsen SS et al (1986) Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 119:1467–1475

    Article  CAS  PubMed  Google Scholar 

  121. Bataille D, Gespach C, Tatemoto K, Marie JC, Coudray AM et al (1981) Bioactive enteroglucagon (oxyntomodulin): present knowledge on its chemical structure and its biological activities. Peptides 2(Suppl 2):41–44

    Article  CAS  PubMed  Google Scholar 

  122. Drucker DJ (2002) Gut adaptation and the glucagon-like peptides. Gut 50:428–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Nauck MA, Bartels E, Orskov C, Ebert R, Creutzfeldt W (1993) Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J Clin Endocrinol Metab 76:912–917

    CAS  PubMed  Google Scholar 

  124. Hansen L, Deacon CF, Orskov C, Holst JJ (1999) Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology 140:5356–5363

    CAS  PubMed  Google Scholar 

  125. Deacon CF, Pridal L, Klarskov L, Olesen M, Holst JJ (1996) Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am J Phys 271:E458–E464

    CAS  Google Scholar 

  126. Wettergren A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J et al (1993) Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 38:665–673

    Article  CAS  PubMed  Google Scholar 

  127. Holmes GM, Browning KN, Tong M, Qualls-Creekmore E, Travagli RA (2009) Vagally mediated effects of glucagon-like peptide 1: in vitro and in vivo gastric actions. J Physiol 587:4749–4759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Plamboeck A, Veedfald S, Deacon CF, Hartmann B, Wettergren A et al (2013) The effect of exogenous GLP-1 on food intake is lost in male truncally vagotomized subjects with pyloroplasty. Am J Physiol Gastrointest Liver Physiol 304:G1117–G1127

    Article  CAS  PubMed  Google Scholar 

  129. Tong J, D’Alessio D (2014) Give the receptor a brake: slowing gastric emptying by GLP-1. Diabetes 63:407–409

    Article  CAS  PubMed  Google Scholar 

  130. Horowitz M, Edelbroek MA, Wishart JM, Straathof JW (1993) Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia 36:857–862

    Article  CAS  PubMed  Google Scholar 

  131. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705

    Article  CAS  PubMed  Google Scholar 

  132. Li Y, Hansotia T, Yusta B, Ris F, Halban PA et al (2003) Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem 278:471–478

    Article  CAS  PubMed  Google Scholar 

  133. Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS et al (2002) Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 87:1239–1246

    Article  CAS  PubMed  Google Scholar 

  134. Scrocchi LA, Brown TJ, MaClusky N, Brubaker PL, Auerbach AB et al (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  CAS  PubMed  Google Scholar 

  135. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM et al (1996) A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379:69–72

    Article  CAS  PubMed  Google Scholar 

  136. Flint A, Raben A, Astrup A, Holst JJ (1998) Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 101:515–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Verdich C, Toubro S, Buemann B, Lysgard Madsen J, Juul Holst J et al (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  CAS  PubMed  Google Scholar 

  138. Naslund E, King N, Mansten S, Adner N, Holst JJ et al (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 

  139. Li L, Shen J, Bala MM, Busse JW, Ebrahim S et al (2014) Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ 348:g2366

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Trujillo JM, Nuffer W, Ellis SL (2015) GLP-1 receptor agonists: a review of head-to-head clinical studies. Ther Adv Endocrinol Metab 6:19–28

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M et al (2008) Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 372:1240–1250

    Article  CAS  PubMed  Google Scholar 

  142. Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C et al (2006) Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 29:2632–2637

    Article  CAS  PubMed  Google Scholar 

  143. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G (2006) Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 29:2638–2643

    Article  CAS  PubMed  Google Scholar 

  144. Yoon KH, Steinberg H, Teng R, Golm GT, Lee M et al (2012) Efficacy and safety of initial combination therapy with sitagliptin and pioglitazone in patients with type 2 diabetes: a 54-week study. Diabetes Obes Metab 14:745–752

    Article  CAS  PubMed  Google Scholar 

  145. Salehi M, Aulinger BA, D'Alessio DA (2008) Targeting beta-cell mass in type 2 diabetes: promise and limitations of new drugs based on incretins. Endocr Rev 29:367–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Zhao H, Wei R, Wang L, Tian Q, Tao M et al (2014) Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner. Am J Physiol Endocrinol Metab 306:E1431–E1441

    Article  CAS  PubMed  Google Scholar 

  147. Cases AI, Ohtsuka T, Kimura H, Zheng B, Shindo K et al (2015) Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer. Oncol Rep 34:1717–1725

    PubMed  Google Scholar 

  148. Bjerre Knudsen L, Madsen LW, Andersen S, Almholt K, de Boer AS et al (2010) Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 151:1473–1486

    Article  PubMed  CAS  Google Scholar 

  149. Chiu WY, Shih SR, Tseng CH (2012) A review on the association between glucagon-like peptide-1 receptor agonists and thyroid cancer. Exp Diabetes Res 2012:924168

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Ligumsky H, Wolf I, Israeli S, Haimsohn M, Ferber S et al (2012) The peptide-hormone glucagon-like peptide-1 activates cAMP and inhibits growth of breast cancer cells. Breast Cancer Res Treat 132:449–461

    Article  CAS  PubMed  Google Scholar 

  151. Nomiyama T, Kawanami T, Irie S, Hamaguchi Y, Terawaki Y et al (2014) Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth. Diabetes 63:3891–3905

    Article  CAS  PubMed  Google Scholar 

  152. Koehler JA, Kain T, Drucker DJ (2011) Glucagon-like peptide-1 receptor activation inhibits growth and augments apoptosis in murine CT26 colon cancer cells. Endocrinology 152:3362–3372

    Article  CAS  PubMed  Google Scholar 

  153. Li Y, Tweedie D, Mattson MP, Holloway HW, Greig NH (2010) Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells. J Neurochem 113:1621–1631

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC (2011) Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 141:150–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Zhao Y, Yang L, Wang X, Zhou Z (2014) The new insights from DPP-4 inhibitors: their potential immune modulatory function in autoimmune diabetes. Diabetes Metab Res Rev 30:646–653

    Article  CAS  PubMed  Google Scholar 

  156. Said SI, Mutt V (1970) Polypeptide with broad biological activity: isolation from small intestine. Science 169:1217–1218

    Article  CAS  PubMed  Google Scholar 

  157. Bloom SR, Polak JM, Pearse AG (1973) Vasoactive intestinal peptide and watery-diarrhoea syndrome. Lancet 2:14–16

    Article  CAS  PubMed  Google Scholar 

  158. Ebeid AM, Murray PD, Fischer JE (1978) Vasoactive intestinal peptide and the watery diarrhea syndrome. Ann Surg 187:411–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Verner JV, Morrison AB (1958) Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. Am J Med 25:374–380

    Article  CAS  PubMed  Google Scholar 

  160. Krejs GJ (1987) VIPoma syndrome. Am J Med 82:37–48

    Article  CAS  PubMed  Google Scholar 

  161. Bloom SR, Yiangou Y, Polak JM (1988) Vasoactive intestinal peptide secreting tumors. Pathophysiological and clinical correlations. Ann N Y Acad Sci 527:518–527

    Article  CAS  PubMed  Google Scholar 

  162. Guzman S, Chayvialle JA, Banks WA, Rayford PL, Thompson JC (1979) Effect of vagal stimulation on pancreatic secretion and on blood levels of gastrin, cholecystokinin, secretin, vasoactive intestinal peptide, and somatostatin. Surgery 86:329–336

    CAS  PubMed  Google Scholar 

  163. Shuttleworth CW, Keef KD (1995) Roles of peptides in enteric neuromuscular transmission. Regul Pept 56:101–120

    Article  CAS  PubMed  Google Scholar 

  164. Tan JS, File TM Jr (1992) Treatment of bacteriuria in pregnancy. Drugs 44:972–980

    Article  CAS  PubMed  Google Scholar 

  165. Chey WA (1993) Hormonal Control of pancreatic Exocrine Secretion. In: Go VLW (ed) The pancreas: biology, pathobiology, and disease, 2nd edn. Raven, New York, pp 403–424

    Google Scholar 

  166. Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A et al (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 164:567–574

    Article  CAS  PubMed  Google Scholar 

  167. Ishihara T, Shigemoto R, Mori K, Takahashi K, Nagata S (1992) Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Neuron 8:811–819

    Article  CAS  PubMed  Google Scholar 

  168. Ichikawa S, Sreedharan SP, Owen RL, Goetzl EJ (1995) Immunochemical localization of type I VIP receptor and NK-1-type substance P receptor in rat lung. Am J Phys 268:L584–L588

    CAS  Google Scholar 

  169. Sreedharan SP, Huang JX, Cheung MC, Goetzl EJ (1995) Structure, expression, and chromosomal localization of the type I human vasoactive intestinal peptide receptor gene. Proc Natl Acad Sci U S A 92:2939–2943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Johnson MC, McCormack RJ, Delgado M, Martinez C, Ganea D (1996) Murine T-lymphocytes express vasoactive intestinal peptide receptor 1 (VIP-R1) mRNA. J Neuroimmunol 68:109–119

    Article  CAS  PubMed  Google Scholar 

  171. Delgado M, Martinez C, Johnson MC, Gomariz RP, Ganea D (1996) Differential expression of vasoactive intestinal peptide receptors 1 and 2 (VIP-R1 and VIP-R2) mRNA in murine lymphocytes. J Neuroimmunol 68:27–38

    Article  CAS  PubMed  Google Scholar 

  172. Usdin TB, Bonner TI, Mezey E (1994) Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology 135:2662–2680

    CAS  PubMed  Google Scholar 

  173. Harmar AJ, Fahrenkrug J, Gozes I, Laburthe M, May V et al (2012) Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 166:4–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Reubi JC, Laderach U, Waser B, Gebbers JO, Robberecht P et al (2000) Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. Cancer Res 60:3105–3112

    CAS  PubMed  Google Scholar 

  175. Reubi JC, Korner M, Waser B, Mazzucchelli L, Guillou L (2004) High expression of peptide receptors as a novel target in gastrointestinal stromal tumours. Eur J Nucl Med Mol Imaging 31:803–810

    Article  CAS  PubMed  Google Scholar 

  176. Berthoud HR, Jeanrenaud B (1982) Sham feeding-induced cephalic phase insulin release in the rat. Am J Phys 242:E280–E285

    CAS  Google Scholar 

  177. Ahren B, Holst JJ (2001) The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50:1030–1038

    Article  CAS  PubMed  Google Scholar 

  178. Havel PJ, Dunning BE, Verchere CB, Baskin DG, O’Dorisio T et al (1997) Evidence that vasoactive intestinal polypeptide is a parasympathetic neurotransmitter in the endocrine pancreas in dogs. Regul Pept 71:163–170

    Article  CAS  PubMed  Google Scholar 

  179. Tornoe K, Hannibal J, Fahrenkrug J, Holst JJ (1997) PACAP-(1-38) as neurotransmitter in pig pancreas: receptor activation revealed by the antagonist PACAP-(6-38). Am J Phys 273:G436–G446

    CAS  Google Scholar 

  180. Filipsson K, Sundler F, Hannibal J, Ahren B (1998) PACAP and PACAP receptors in insulin producing tissues: localization and effects. Regul Pept 74:167–175

    Article  CAS  PubMed  Google Scholar 

  181. Asnicar MA, Koster A, Heiman ML, Tinsley F, Smith DP et al (2002) Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating peptide receptor 2 deficiency in mice results in growth retardation and increased basal metabolic rate. Endocrinology 143:3994–4006

    Article  CAS  PubMed  Google Scholar 

  182. Tsutsumi M, Claus TH, Liang Y, Li Y, Yang L et al (2002) A potent and highly selective VPAC2 agonist enhances glucose-induced insulin release and glucose disposal: a potential therapy for type 2 diabetes. Diabetes 51:1453–1460

    Article  CAS  PubMed  Google Scholar 

  183. Bertrand G, Puech R, Maisonnasse Y, Bockaert J, Loubatieres-Mariani MM (1996) Comparative effects of PACAP and VIP on pancreatic endocrine secretions and vascular resistance in rat. Br J Pharmacol 117:764–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Yada T, Sakurada M, Ihida K, Nakata M, Murata F et al (1994) Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet beta-cells. J Biol Chem 269:1290–1293

    CAS  PubMed  Google Scholar 

  185. Filipsson K, Tornoe K, Holst J, Ahren B (1997) Pituitary adenylate cyclase-activating polypeptide stimulates insulin and glucagon secretion in humans. J Clin Endocrinol Metab 82:3093–3098

    CAS  PubMed  Google Scholar 

  186. Filipsson K, Holst JJ, Ahren B (2000) PACAP contributes to insulin secretion after gastric glucose gavage in mice. Am J Physiol Regul Integr Comp Physiol 279:R424–R432

    CAS  PubMed  Google Scholar 

  187. Adams BA, Gray SL, Isaac ER, Bianco AC, Vidal-Puig AJ et al (2008) Feeding and metabolism in mice lacking pituitary adenylate cyclase-activating polypeptide. Endocrinology 149:1571–1580

    Article  CAS  PubMed  Google Scholar 

  188. Baranowska B, Radzikowska M, Wasilewska-Dziubinska E, Roguski K, Borowiec M (2000) Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity. Diabetes Obes Metab 2:99–103

    Article  CAS  PubMed  Google Scholar 

  189. Tomkin GH, Ardill J, Lafferty H, Darragh A (1983) Vasoactive intestinal polypeptide in obesity. Int J Obes 7:153–160

    CAS  PubMed  Google Scholar 

  190. Gardner DF, Kilberg MS, Wolfe MM, McGuigan JE, Misbin RI (1985) Preferential binding of vasoactive intestinal peptide to hepatic nonparenchymal cells. Am J Phys 248:G663–G669

    CAS  Google Scholar 

  191. Kellum JM, Kuemmerle JF, O'Dorisio TM, Rayford P, Martin D et al (1990) Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty. Ann Surg 211:763–770, discussion 770-761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Vu JP, Larauche M, Flores M, Luong L, Norris J et al (2015) Regulation of appetite, body composition, and metabolic hormones by Vasoactive Intestinal Polypeptide (VIP). J Mol Neurosci 56:377–387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Ivy AC, Oldberg E (1928) A hormone mechanism for gall-bladder contraction and evacuation. Am J Physiol 86:599–613

    CAS  Google Scholar 

  194. Harper AA, Raper HS (1943) Pancreozymin, a stimulant of the secretion of pancreatic enzymes in extracts of the small intestine. J Physiol 102:115–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  196. Smith GP, Jerome C, Cushin BJ, Eterno R, Simansky KJ (1981) Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science 213:1036–1037

    Article  CAS  PubMed  Google Scholar 

  197. Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA (1985) Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest 75:1144–1152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Covasa M, Ritter RC (2001) Attenuated satiation response to intestinal nutrients in rats that do not express CCK-A receptors. Peptides 22:1339–1348

    Article  CAS  PubMed  Google Scholar 

  199. Wank SA (1998) G protein-coupled receptors in gastrointestinal physiology. I CCK receptors: an exemplary family. Am J Physiol 274:G607–G613

    CAS  PubMed  Google Scholar 

  200. Date Y, Toshinai K, Koda S, Miyazato M, Shimbara T et al (2005) Peripheral interaction of ghrelin with cholecystokinin on feeding regulation. Endocrinology 146:3518–3525

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  202. Lieverse RJ, Jansen JB, Masclee AM, Lamers CB (1994) Satiety effects of cholecystokinin in humans. Gastroenterology 106:1451–1454

    Article  CAS  PubMed  Google Scholar 

  203. Feinle C, D'Amato M, Read NW (1996) Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid. Gastroenterology 110:1379–1385

    Article  CAS  PubMed  Google Scholar 

  204. Lieverse RJ, Masclee AA, Jansen JB, Rovati LC, Lamers CB (1995) Satiety effects of the type A CCK receptor antagonist loxiglumide in lean and obese women. Biol Psychiatry 37:331–335

    Article  CAS  PubMed  Google Scholar 

  205. Takiguchi S, Suzuki S, Sato Y, Kanai S, Miyasaka K et al (2002) Role of CCK-A receptor for pancreatic function in mice: a study in CCK-A receptor knockout mice. Pancreas 24:276–283

    Article  PubMed  Google Scholar 

  206. Baldwin GS, Shulkes A (2007) CCK receptors and cancer. Curr Top Med Chem 7:1232–1238

    Article  CAS  PubMed  Google Scholar 

  207. Smith JP, Kramer ST, Solomon TE (1991) CCK stimulates growth of six human pancreatic cancer cell lines in serum-free medium. Regul Pept 32:341–349

    Article  CAS  PubMed  Google Scholar 

  208. Sethi T, Rozengurt E (1991) Multiple neuropeptides stimulate clonal growth of small cell lung cancer: effects of bradykinin, vasopressin, cholecystokinin, galanin, and neurotensin. Cancer Res 51:3621–3623

    CAS  PubMed  Google Scholar 

  209. Behe M, Behr TM (2002) Cholecystokinin-B (CCK-B)/gastrin receptor targeting peptides for staging and therapy of medullary thyroid cancer and other CCK-B receptor expressing malignancies. Biopolymers 66:399–418

    Article  CAS  PubMed  Google Scholar 

  210. Kimmel JR, Hayden LJ, Pollock HG (1975) Isolation and characterization of a new pancreatic polypeptide hormone. J Biol Chem 250:9369–9376

    CAS  PubMed  Google Scholar 

  211. Ueno N, Inui A, Iwamoto M, Kaga T, Asakawa A et al (1999) Decreased food intake and body weight in pancreatic polypeptide-overexpressing mice. Gastroenterology 117:1427–1432

    Article  CAS  PubMed  Google Scholar 

  212. Katsuura G, Asakawa A, Inui A (2002) Roles of pancreatic polypeptide in regulation of food intake. Peptides 23:323–329

    Article  CAS  PubMed  Google Scholar 

  213. Adrian TE, Besterman HS, Cooke TJ, Bloom SR, Barnes AJ et al (1977) Mechanism of pancreatic polypeptide release in man. Lancet 1:161–163

    Article  CAS  PubMed  Google Scholar 

  214. Inui A, Okita M, Miura M, Hirosue Y, Mizuno N et al (1993) Plasma and cerebroventricular fluid levels of pancreatic polypeptide in the dog: effects of feeding, insulin-induced hypoglycemia, and physical exercise. Endocrinology 132:1235–1239

    CAS  PubMed  Google Scholar 

  215. Sive AA, Vinik AI, van Tonder SV (1979) Pancreatic polypeptide (PP) responses to oral and intravenous glucose in man. Am J Gastroenterol 71:183–185

    CAS  PubMed  Google Scholar 

  216. Taylor IL, Impicciatore M, Carter DC, Walsh JH (1978) Effect of atropine and vagotomy on pancreatic polypeptide response to a meal in dogs. Am J Phys 235:E443–E447

    CAS  Google Scholar 

  217. Schwartz TW, Holst JJ, Fahrenkrug J, Jensen SL, Nielsen OV et al (1978) Vagal, cholinergic regulation of pancreatic polypeptide secretion. J Clin Invest 61:781–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Gehlert DR (1998) Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological implications. Proc Soc Exp Biol Med 218:7–22

    Article  CAS  PubMed  Google Scholar 

  219. Wahlestedt C, Reis DJ (1993) Neuropeptide Y-related peptides and their receptors--are the receptors potential therapeutic drug targets? Annu Rev Pharmacol Toxicol 33:309–352

    Article  CAS  PubMed  Google Scholar 

  220. Alkemade A, Yi CX, Pei L, Harakalova M, Swaab DF et al (2012) AgRP and NPY expression in the human hypothalamic infundibular nucleus correlate with body mass index, whereas changes in alphaMSH are related to type 2 diabetes. J Clin Endocrinol Metab 97:E925–E933

    Article  CAS  PubMed  Google Scholar 

  221. Spinazzi R, Andreis PG, Nussdorfer GG (2005) Neuropeptide-Y and Y-receptors in the autocrine-paracrine regulation of adrenal gland under physiological and pathophysiological conditions (Review). Int J Mol Med 15:3–13

    CAS  PubMed  Google Scholar 

  222. Hazelwood RL (1993) The pancreatic polypeptide (PP-fold) family: gastrointestinal, vascular, and feeding behavioral implications. Proc Soc Exp Biol Med 202:44–63

    Article  CAS  PubMed  Google Scholar 

  223. Huda MS, Wilding JP, Pinkney JH (2006) Gut peptides and the regulation of appetite. Obes Rev 7:163–182

    Article  CAS  PubMed  Google Scholar 

  224. Lassmann V, Vague P, Vialettes B, Simon MC (1980) Low plasma levels of pancreatic polypeptide in obesity. Diabetes 29:428–430

    Article  CAS  PubMed  Google Scholar 

  225. 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  CAS  PubMed  Google Scholar 

  226. Uhe AM, Szmukler GI, Collier GR, Hansky J, O'Dea K et al (1992) Potential regulators of feeding behavior in anorexia nervosa. Am J Clin Nutr 55:28–32

    CAS  PubMed  Google Scholar 

  227. Alderdice JT, Dinsmore WW, Buchanan KD, Adams C (1985) Gastrointestinal hormones in anorexia nervosa. J Psychiatr Res 19:207–213

    Article  CAS  PubMed  Google Scholar 

  228. Glaser B, Zoghlin G, Pienta K, Vinik AI (1988) Pancreatic polypeptide response to secretin in obesity: effects of glucose intolerance. Horm Metab Res 20:288–292

    Article  CAS  PubMed  Google Scholar 

  229. Schrumpf E, Linnestad P, Nygaard K, Giercksky KE, Fausa O (1981) Pancreatic polypeptide secretion before and after gastric bypass surgery for morbid obesity. Scand J Gastroenterol 16:1009–1014

    Article  CAS  PubMed  Google Scholar 

  230. Swarbrick MM, Stanhope KL, Austrheim-Smith IT, Van Loan MD, Ali MR et al (2008) Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery. Diabetologia 51:1901–1911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Meryn S, Stein D, Straus EW (1986) Fasting- and meal-stimulated peptide hormone concentrations before and after gastric surgery for morbid obesity. Metab Clin Exp 35:798–802

    Article  CAS  PubMed  Google Scholar 

  232. Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G et al (2003) Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 124:1325–1336

    Article  CAS  PubMed  Google Scholar 

  233. Tan TM, Field BC, Minnion JS, Cuenco-Shillito J, Chambers ES et al (2012) Pharmacokinetics, adverse effects and tolerability of a novel analogue of human pancreatic polypeptide, PP 1420. Br J Clin Pharmacol 73:232–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Tomita T, Kimmel JR, Friesen SR, Doull V, Pollock HG (1985) Pancreatic polypeptide in islet cell tumors. Morphologic and functional correlations. Cancer 56:1649–1657

    Article  CAS  PubMed  Google Scholar 

  235. Bellows C, Haque S, Jaffe B (1998) Pancreatic polypeptide islet cell tumor: case report and review of the literature. J Gastrointest Surg 2:526–532

    Article  CAS  PubMed  Google Scholar 

  236. Kuo SC, Gananadha S, Scarlett CJ, Gill A, Smith RC (2008) Sporadic pancreatic polypeptide secreting tumors (PPomas) of the pancreas. World J Surg 32:1815–1822

    Article  PubMed  Google Scholar 

  237. Tatemoto K (1982) Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion. Proc Natl Acad Sci U S A 79:2514–2518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Lundberg JM, Tatemoto K, Terenius L, Hellstrom PM, Mutt V et al (1982) Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc Natl Acad Sci U S A 79:4471–4475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Essah PA, Levy JR, Sistrun SN, Kelly SM, Nestler JE (2007) Effect of macronutrient composition on postprandial peptide YY levels. J Clin Endocrinol Metab 92:4052–4055

    Article  CAS  PubMed  Google Scholar 

  240. Cooper JA (2014) Factors affecting circulating levels of peptide YY in humans: a comprehensive review. Nutr Res Rev 27:186–197

    Article  CAS  PubMed  Google Scholar 

  241. Helou N, Obeid O, Azar ST, Hwalla N (2008) Variation of postprandial PYY 3-36 response following ingestion of differing macronutrient meals in obese females. Ann Nutr Metab 52:188–195

    Article  CAS  PubMed  Google Scholar 

  242. Batterham RL, Bloom SR (2003) The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci 994:162–168

    Article  CAS  PubMed  Google Scholar 

  243. Gueugnon C, Mougin F, Nguyen NU, Bouhaddi M, Nicolet-Guenat M et al (2012) Ghrelin and PYY levels in adolescents with severe obesity: effects of weight loss induced by long-term exercise training and modified food habits. Eur J Appl Physiol 112:1797–1805

    Article  CAS  PubMed  Google Scholar 

  244. Pfluger PT, Kampe J, Castaneda TR, Vahl T, D’Alessio DA et al (2007) Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36. J Clin Endocrinol Metab 92:583–588

    Article  CAS  PubMed  Google Scholar 

  245. Olivan B, Teixeira J, Bose M, Bawa B, Chang T et al (2009) Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 levels. Ann Surg 249:948–953

    Article  PubMed  PubMed Central  Google Scholar 

  246. le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F et al (2006) Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 243:108–114

    Article  PubMed  PubMed Central  Google Scholar 

  247. Chan JL, Mun EC, Stoyneva V, Mantzoros CS, Goldfine AB (2006) Peptide YY levels are elevated after gastric bypass surgery. Obesity 14:194–198

    Article  CAS  PubMed  Google Scholar 

  248. Morinigo R, Vidal J, Lacy AM, Delgado S, Casamitjana R et al (2008) Circulating peptide YY, weight loss, and glucose homeostasis after gastric bypass surgery in morbidly obese subjects. Ann Surg 247:270–275

    Article  PubMed  Google Scholar 

  249. Moriya R, Mashiko S, Ishihara A, Takahashi T, Murai T et al (2009) Comparison of independent and combined chronic anti-obese effects of NPY Y2 receptor agonist, PYY(3-36), and NPY Y5 receptor antagonist in diet-induced obese mice. Peptides 30:1318–1322

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  251. Ortiz AA, Milardo LF, DeCarr LB, Buckholz TM, Mays MR et al (2007) A novel long-acting selective neuropeptide Y2 receptor polyethylene glycol-conjugated peptide agonist reduces food intake and body weight and improves glucose metabolism in rodents. J Pharmacol Exp Ther 323:692–700

    Article  CAS  PubMed  Google Scholar 

  252. Chandarana K, Gelegen C, Irvine EE, Choudhury AI, Amouyal C et al (2013) Peripheral activation of the Y2-receptor promotes secretion of GLP-1 and improves glucose tolerance. Mol Metab 2:142–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Moriya R, Shirakura T, Hirose H, Kanno T, Suzuki J et al (2010) NPY Y2 receptor agonist PYY(3-36) inhibits diarrhea by reducing intestinal fluid secretion and slowing colonic transit in mice. Peptides 31:671–675

    Article  CAS  PubMed  Google Scholar 

  254. Iwafuchi M, Watanabe H, Ishihara N, Shimoda T, Iwashita A et al (1986) Peptide YY immunoreactive cells in gastrointestinal carcinoids: immunohistochemical and ultrastructural studies of 60 tumors. Hum Pathol 17:291–296

    Article  CAS  PubMed  Google Scholar 

  255. Motoyama T, Katayama Y, Watanabe H, Okazaki E, Shibuya H (1992) Functioning ovarian carcinoids induce severe constipation. Cancer 70:513–518

    Article  CAS  PubMed  Google Scholar 

  256. Matsuda K, Maehama T, Kanazawa K (2002) Strumal carcinoid tumor of the ovary: a case exhibiting severe constipation associated with PYY. Gynecol Oncol 87:143–145

    Article  PubMed  Google Scholar 

  257. Vona-Davis L, McFadden DW (2007) PYY and the pancreas: inhibition of tumor growth and inflammation. Peptides 28:334–338

    Article  CAS  PubMed  Google Scholar 

  258. Liu CD, Slice LW, Balasubramaniam A, Walsh JH, Newton TR et al (1995) Y2 receptors decrease human pancreatic cancer growth and intracellular cyclic adenosine monophosphate levels. Surgery 118:229–235, discussion 235-226

    Article  CAS  PubMed  Google Scholar 

  259. Moschovi M, Trimis G, Vounatsou M, Katsibardi K, Margeli A et al (2008) Serial plasma concentrations of PYY and ghrelin during chemotherapy in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 30:733–737

    Article  CAS  PubMed  Google Scholar 

  260. Edkins JS (1906) The chemical mechanism of gastric secretion. J Physiol 34:133–144

    Article  PubMed  PubMed Central  Google Scholar 

  261. Wolfe MM, Sachs G (2000) Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology 118:S9–S31

    Article  CAS  PubMed  Google Scholar 

  262. Waldum HL, Sandvik AK, Brenna E, Petersen H (1991) Gastrin-histamine sequence in the regulation of gastric acid secretion. Gut 32:698–701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Seva C, Dickinson CJ, Yamada T (1994) Growth-promoting effects of glycine-extended progastrin. Science 265:410–412

    Article  CAS  PubMed  Google Scholar 

  264. Dockray G, Dimaline R, Varro A (2005) Gastrin: old hormone, new functions. Pflugers Arch - Eur J Physiol 449:344–355

    Article  CAS  Google Scholar 

  265. Kopin AS, Lee YM, McBride EW, Miller LJ, Lu M et al (1992) Expression cloning and characterization of the canine parietal cell gastrin receptor. Proc Natl Acad Sci U S A 89:3605–3609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  266. Watson SA, Grabowska AM, El-Zaatari M, Takhar A (2006) Gastrin – active participant or bystander in gastric carcinogenesis? Nat Rev Cancer 6:936–946

    Article  CAS  PubMed  Google Scholar 

  267. Wolfe MM, Song DH, Jepeal LI, Moore TC (2003) Gastrin peptides: pathophysiologic role in gastrointestinal carcinogenesis. Curr Opin Endocrinol Diabetes Obes 10:39–49

    Article  CAS  Google Scholar 

  268. Bordi C, Cocconi G, Togni R, Vezzadini P, Missale G (1974) Gastric endocrine cell proliferation. Association with Zollinger-Ellison syndrome. Arch Pathol 98:274–278

    CAS  PubMed  Google Scholar 

  269. Song H, Zhu J, Lu D (2014) Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions. Cochrane Database Syst Rev 12, CD010623

    Google Scholar 

  270. Bordi C, D'Adda T, Azzoni C, Pilato FP, Caruana P (1995) Hypergastrinemia and gastric enterochromaffin-like cells. Am J Surg Pathol 19(Suppl 1):S8–S19

    PubMed  Google Scholar 

  271. Burkitt MD, Pritchard DM (2006) Review article: pathogenesis and management of gastric carcinoid tumours. Aliment Pharmacol Ther 24:1305–1320

    Article  CAS  PubMed  Google Scholar 

  272. Thorburn CM, Friedman GD, Dickinson CJ, Vogelman JH, Orentreich N et al (1998) Gastrin and colorectal cancer: a prospective study. Gastroenterology 115:275–280

    Article  CAS  PubMed  Google Scholar 

  273. Koh TJ, Dockray GJ, Varro A, Cahill RJ, Dangler CA et al (1999) Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation. J Clin Invest 103:1119–1126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Koh TJ, Goldenring JR, Ito S, Mashimo H, Kopin AS et al (1997) Gastrin deficiency results in altered gastric differentiation and decreased colonic proliferation in mice. Gastroenterology 113:1015–1025

    Article  CAS  PubMed  Google Scholar 

  275. Kolligs FT, Bommer G, Goke B (2002) Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion 66:131–144

    Article  CAS  PubMed  Google Scholar 

  276. Song DH, Kaufman JC, Borodyansky L, Albanese C, Pestell RG et al (2005) Gastrin stabilises beta-catenin protein in mouse colorectal cancer cells. Br J Cancer 92:1581–1587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Chang AJ, Song DH, Wolfe MM (2006) Attenuation of peroxisome proliferator-activated receptor gamma (PPARgamma) mediates gastrin-stimulated colorectal cancer cell proliferation. J Biol Chem 281:14700–14710

    Article  CAS  PubMed  Google Scholar 

  278. Gibbs J, Smith GP (1988) The actions of bombesin-like peptides on food intake. Ann N Y Acad Sci 547:210–216

    Article  CAS  PubMed  Google Scholar 

  279. Muurahainen NE, Kissileff HR, Pi-Sunyer FX (1993) Intravenous infusion of bombesin reduces food intake in humans. Am J Phys 264:R350–R354

    CAS  Google Scholar 

  280. Hampton LL, Ladenheim EE, Akeson M, Way JM, Weber HC et al (1998) Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice. Proc Natl Acad Sci U S A 95:3188–3192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  281. Ohki-Hamazaki H, Sakai Y, Kamata K, Ogura H, Okuyama S et al (1999) Functional properties of two bombesin-like peptide receptors revealed by the analysis of mice lacking neuromedin B receptor. J Neurosci 19:948–954

    CAS  PubMed  Google Scholar 

  282. Wada E, Watase K, Yamada K, Ogura H, Yamano M et al (1997) Generation and characterization of mice lacking gastrin-releasing peptide receptor. Biochem Biophys Res Commun 239:28–33

    Article  CAS  PubMed  Google Scholar 

  283. Ohki-Hamazaki H, Watase K, Yamamoto K, Ogura H, Yamano M et al (1997) Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature 390:165–169

    Article  CAS  PubMed  Google Scholar 

  284. Majumdar ID, Weber HC (2012) Biology and pharmacology of bombesin receptor subtype-3. Curr Opin Endocrinol Diabetes Obes 19:3–7

    Article  CAS  PubMed  Google Scholar 

  285. Guan XM, Chen H, Dobbelaar PH, Dong Y, Fong TM et al (2010) Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity. Cell Metab 11:101–112

    Article  CAS  PubMed  Google Scholar 

  286. Moody TW, Pert CB, Gazdar AF, Carney DN, Minna JD (1981) High levels of intracellular bombesin characterize human small-cell lung carcinoma. Science 214:1246–1248

    Article  CAS  PubMed  Google Scholar 

  287. Erisman MD, Linnoila RI, Hernandez O, DiAugustine RP, Lazarus LH (1982) Human lung small-cell carcinoma contains bombesin. Proc Natl Acad Sci U S A 79:2379–2383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  288. Cuttitta F, Carney DN, Mulshine J, Moody TW, Fedorko J et al (1985) Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316:823–826

    Article  CAS  PubMed  Google Scholar 

  289. Reubi JC, Wenger S, Schmuckli-Maurer J, Schaer JC, Gugger M (2002) Bombesin receptor subtypes in human cancers: detection with the universal radioligand (125)I-[D-TYR(6), beta-ALA(11), PHE(13), NLE(14)] bombesin(6-14). Clin CancerRes 8:1139–1146

    CAS  Google Scholar 

  290. Pansky A, De Weerth A, Fasler-Kan E, Boulay JL, Schulz M et al (2000) Gastrin releasing peptide-preferring bombesin receptors mediate growth of human renal cell carcinoma. J Am Soc Nephrol 11:1409–1418

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hematology/Oncology, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA

    Debora S. Bruno M.D

  2. Case Western Reserve University, Cleveland, OH, USA

    Debora S. Bruno M.D

  3. Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA

    Debora S. Bruno M.D & M. Michael Wolfe M.D

Authors
  1. Debora S. Bruno M.D
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Michael Wolfe M.D
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Debora S. Bruno M.D .

Editor information

Editors and Affiliations

  1. Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA

    Ofer Reizes

  2. Center for Science, Health and Society, Case Western Reserve University, Cleveland, Ohio, USA

    Nathan A. Berger

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bruno, D.S., Wolfe, M.M. (2017). GI Peptides, Energy Balance, and Cancer. In: Reizes, O., Berger, N. (eds) Adipocytokines, Energy Balance, and Cancer. Energy Balance and Cancer, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-41677-9_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-41677-9_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-41675-5

  • Online ISBN: 978-3-319-41677-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation