Neonatology pp 281-289 | Cite as

Hormones and Gastrointestinal Function

  • Flavia Prodam
  • Simonetta Bellone
  • Silvia Savastio
  • Arianna Busti
  • Carla Guidi
  • Alice Monzani
  • Gianni Bona


Development is a continuous process. Nutrition, environment and stress modulate development through gene expression in an epigenetic manner. Prenatal and perinatal nutrition can be imprinting factors and turn on different genes that provide different phenotypes, such as the thrifty phenotype [1]. Indeed, the nutritional support of gastrointestinal growth and function is an important tool in the clinical care of newborn babies, in particular preterm neonates. Before birth, although amniotic fluid is not the main source of nutrition for the fetus, it contributes up to 15% of fetal nutritional requirements and plays a key role in its development and maturation [2, 3]. Accordingly, by 20 weeks of gestation, the anatomy of the fetal gut resembles that of the term neonate. However, the process of intestinal absorption is only partially mature before 26 weeks of gestation: gastro-entero-pancreatic peptides are secreted at a basal rate and can be completely stimulated or inhibited after delivery, in particular through contact with nutrients [4, 5]. At the age of 2 years, the intestine is fully functional [6]. Gut hormones, peptides, and growth factors clearly have a role in gut growth after birth and directly and indirectly mediate the trophic actions of enteral nutrition in a manner that is still incompletely understood [5]. By contrast, hormones and growth factors, which are present in breast milk, also seem to exert trophic activities on gut development and immune function. The interplay is complex [1, 3]. Little is known about the development of these regulatory systems in the human neonate and, as a consequence, premature infants experience significant morbidity and mortality associated with feeding problems [6]. Present clinical nutritional support for preterm babies consists of enteral and parenteral nutrition but both have associated complications [6, 7]. Since enteral feeding is important for gut development, acute or chronic gastrointestinal diseases could be caused by feeding with formula rather than human breast milk. Formula milks contain higher amounts of proteins and lack many endogenous hormones and growth factors [5, 6, 8]. A better understanding of factors linked to gastrointestinal function and energy metabolism could result in improved strategies for supporting nutrition of preterm newborns as well as their later development.


Ghrelin Level Preterm Neonate Preterm Newborn Total Ghrelin Level Migrate Motor Complex Activity 
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  1. 1.
    de Moura EG, Lisboa PC, Passos MC (2008) Neonatal programming of neuroimmunomodulation - role of adipocytokines and neuropeptides. Neuroimmunomodulation 15: 176–188PubMedGoogle Scholar
  2. 2.
    Mulvihill SJ, Stone MM, Debas HT, Fonkalsrud EW (1985) The role of amniotic fluid in fetal nutrition. J Pediatr Surg 20: 668–672PubMedGoogle Scholar
  3. 3.
    Wagner CL (2002) Amniotic fluid and human milk: a continuum of effect? J Pediatr Gastroenterol Nutr 34: 513–514PubMedGoogle Scholar
  4. 4.
    Lebenthal A, Lebenthal E (1999) The ontogeny of the small intestinal epithelium. JPEN J Parenter Enteral Nutr 23: S3–S6PubMedGoogle Scholar
  5. 5.
    Burrin DG, Stoll B (2002) Key nutrients and growth factors for the neonatal gastrointestinal tract. Clin Perinatol 29: 65–96PubMedGoogle Scholar
  6. 6.
    Corpeleijn WE, van Vliet I, de Gast-Bakker DA et al (2008) Effect of enteral IGF-1 supplementation on feeding tolerance, growth, and gut permeability in enterally fed premature neonates. J Pediatr Gas-troenterol Nutr 46: 184–190Google Scholar
  7. 7.
    Amin H, Holst JJ, Hartmann B et al (2008) Functional ontogeny of the proglucagon-derived peptide axis in the premature human neonate. Pediatrics 121: e180–e186PubMedGoogle Scholar
  8. 8.
    Agostoni C (2005) Ghrelin, leptin and the neurometabolic axis of breastfed and formula-fed infants. Acta Paediatr 94: 523–525PubMedGoogle Scholar
  9. 9.
    Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiol Rev 87: 1409–1439PubMedGoogle Scholar
  10. 10.
    Neary NM, Goldstone AP Bloom SR (2004) Appetite regulation: from the gut to the hypothalamus. Clin Endocrinol 60: 153–160Google Scholar
  11. 11.
    Hellstrom PM, Geliebter A, Naslund E et al (2004) Peripheral and central signals in the control of eating in normal, obese and binge- eating human subjects. Br J Nutr 92 (Suppl 1): S47–S57PubMedGoogle Scholar
  12. 12.
    Vilsboll T, Krarup T, Sonne J et al (2003) Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 88: 2706–2713PubMedGoogle Scholar
  13. 13.
    Naslund E, Barkeling B, King N et al (1999) Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 23: 304–311PubMedGoogle Scholar
  14. 14.
    Verdich C, Flint A, Gutzwiller JP et al (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 - 4389PubMedGoogle Scholar
  15. 15.
    Drucker DJ (2002) Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology 122: 531–544PubMedGoogle Scholar
  16. 16.
    Konturek SJ, Konturek JW, Pawlik T, Brzozowski T (2004) Brain- gut axis and its role in the control of food intake. J Physiol Pharmacol 55: 137–154PubMedGoogle Scholar
  17. 17.
    Schou JH, Pilgaard K, Vilsboll T et al (2005) Normal secretion and action of the gut incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in young men with low birth weight. J Clin Endocrinol Metab 90: 4912–4919PubMedGoogle Scholar
  18. 18.
    Lovshin J, Drucker DJ (2000) New frontiers in the biology of GLP- 2. Regul Pept 90: 27–32PubMedGoogle Scholar
  19. 19.
    Xiao Q, Boushey RP Drucker DJ, Brubaker PL (1999) Secretion of the intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans. Gastroenterology 117: 99–105PubMedGoogle Scholar
  20. 20.
    Tang-Christensen M, Larsen PJ, Thulesen J et al (2000) The pro- glucagon-derived peptide, glucagon-like peptide-2, is a neuro- transmitter involved in the regulation of food intake. Nat Med 6: 802–807PubMedGoogle Scholar
  21. 21.
    Schmidt PT, Naslund E, Gryback P et al (2003) Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety. Regul Pept 116: 21–25PubMedGoogle Scholar
  22. 22.
    Martin GR, Beck PL, Sigalet DL (2006) Gut hormones, and short bowel syndrome: the enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation. World J Gastroenterol 12: 4117–4129PubMedGoogle Scholar
  23. 23.
    Garcia-Diaz D, Campion J, Milagro FI, Martinez JA (2007) Adi-posity dependent apelin gene expression: relationships with oxidative and inflammation markers. Mol Cell Biochem 305: 87–94PubMedGoogle Scholar
  24. 24.
    Hill ME, Asa SL, Drucker DJ (1999) Essential requirement for Pax6 in control of enteroendocrine proglucagon gene transcription. Mol Endocrinol 13: 1474–1486PubMedGoogle Scholar
  25. 25.
    Yoshikawa H, Miyata I, Eto Y (2006) Serum glucagon-like pep- tide-2 levels in neonates: comparison between extremely low-birth- weight infants and normal-term infants. Pediatr Int 48: 464–469PubMedGoogle Scholar
  26. 26.
    Lambeir AM, Durinx C, Scharpe S, De Meester I (2003) Dipep- tidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 40: 209–294PubMedGoogle Scholar
  27. 27.
    Sigalet DL, Martin G, Meddings J et al (2004) GLP-2 levels in infants with intestinal dysfunction. Pediatr Res 56: 371–376PubMedGoogle Scholar
  28. 28.
    Cohen MA, Ellis SM, le Roux CW et al (2003) Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin En- docrinol Metab 88: 4696–4701Google Scholar
  29. 29.
    Chaudhri OB, Wynne K, Bloom SR (2008) Can gut hormones control appetite and prevent obesity? Diabetes Care 31 (Suppl 2): S284–S289PubMedGoogle Scholar
  30. 30.
    Gardiner JV, Jayasena CN, Bloom SR (2008) Gut hormones: a weight off your mind. J Neuroendocrinol 20: 834–841PubMedGoogle Scholar
  31. 31.
    Dakin CL, Gunn I, Small CJ et al (2001) Oxyntomodulin inhibits food intake in the rat. Endocrinology 142: 4244–4250PubMedGoogle Scholar
  32. 32.
    Dakin CL, Small CJ, Batterham RL et al (2004) Peripheral oxyn-tomodulin reduces food intake and body weight gain in rats. Endocrinology 145: 2687–2695PubMedGoogle Scholar
  33. 33.
    Wynne K, Park AJ, Small CJ et al (2006) Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J Obes 30: 1729–1736Google Scholar
  34. 34.
    Mechanick JI, Kushner RF, Sugerman HJ et al (2008) American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical guidelines for clinical practice for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient. Endocr Pract 14 (Suppl 1): 1–83PubMedGoogle Scholar
  35. 35.
    Ranganath LR (2008) The entero-insular axis: implications for human metabolism. Clin Chem Lab Med 46: 43–56PubMedGoogle Scholar
  36. 36.
    Ranganath LR (2008) Incretins: pathophysiological and therapeutic implications of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. J Clin Pathol 61: 401–409PubMedGoogle Scholar
  37. 37.
    Flatt PR (2007) Effective surgical treatment of obesity may be mediated by ablation of the lipogenic gut hormone gastric inhibitory polypeptide (GIP): evidence and clinical opportunity for development of new obesity-diabetes drugs? Diab Vasc Dis Res 4: 151–153PubMedGoogle Scholar
  38. 38.
    Lu M, Wheeler MB, Leng XH, Boyd AE (1993) Stimulation of insulin secretion and insulin gene expression by gastric inhibitory polypeptide. Trans Assoc Am Physicians 106: 42–53PubMedGoogle Scholar
  39. 39.
    Jia X, Brown JC, Ma P et al (1995) Effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-I-(7-36) on insulin secretion. Am J Physiol 268: E645–E651PubMedGoogle Scholar
  40. 40.
    Naitoh R, Miyawaki K, Harada N et al (2008) Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in mice. Biochem Biophys Res Commun 376: 21–25PubMedGoogle Scholar
  41. 41.
    Althage MC, Ford EL, Wang S et al (2008) Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet. J Biol Chem 283: 18365–18376PubMedGoogle Scholar
  42. 42.
    Gault VA, Irwin N, Green BD 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: 2436–2446PubMedGoogle Scholar
  43. 43.
    Flatt PR (2008) Dorothy Hodgkin Lecture 2008. Gastric inhibitory polypeptide (GIP) revisited: a new therapeutic target for obesity- diabetes? Diabet Med 25: 759–764PubMedGoogle Scholar
  44. 44.
    Heptulla RA, Tamborlane WV, Cavaghan M et al (2000) Augmen¬tation of alimentary insulin secretion despite similar gastric inhibitory peptide ( GIP) responses in juvenile obesity. Pediatr Res 47: 628–633Google Scholar
  45. 45.
    Stock S, Leichner P, Wong AC et al (2005) Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger re-sponses to a mixed meal in anorexic, obese, and control female adolescents. J Clin Endocrinol Metab 90: 2161 - 2168PubMedGoogle Scholar
  46. 46.
    Higgins PB, Fernandez JR, Garvey WT et al (2008) Entero-insular axis and postprandial insulin differences in African American and European American children. Am J Clin Nutr 88: 1277–1283PubMedGoogle Scholar
  47. 47.
    Knip M, Kaapa P, Koivisto M (1993) Hormonal enteroinsular axis in newborn infants of insulin-treated diabetic mothers. J Clin En- docrinol Metab 77: 1340–1344Google Scholar
  48. 48.
    Lucas A, Sarson DL, Bloom SR, Aynsley-Green A (1980) Developmental aspects of gastric inhibitory polypeptide ( GIP) and its possible role in the enteroinsular axis in neonates. Acta Paediatr Scand 69: 321–325Google Scholar
  49. 49.
    King KC, Oliven A, Kalhan SC (1989) Functional enteroinsular axis in full-term newborn infants. Pediatr Res 25: 490–495PubMedGoogle Scholar
  50. 50.
    Fallucca F, Kuhl C, Lauritsen KB et al (1985) Gastric inhibitory polypeptide ( GIP) concentration in human amniotic fluid. Horm Metab Res 17: 251–255PubMedGoogle Scholar
  51. 51.
    Heijboer AC, Pijl H, Van den Hoek AM et al (2006) Gut-brain axis: regulation of glucose metabolism. J Neuroendocrinol 18: 883–894PubMedGoogle Scholar
  52. 52.
    Batterham RL, Cowley MA, Small CJ et al (2002) Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418: 650–654PubMedGoogle Scholar
  53. 53.
    Degen L, Oesch S, Casanova M et al (2005) Effect of peptide YY3- 36 on food intake in humans. Gastroenterology 129: 1430–1436PubMedGoogle Scholar
  54. 54.
    Van den Hoek AM, Heijboer AC, Corssmit EP et al (2004) PYY3- 36 reinforces insulin action on glucose disposal in mice fed a high- fat diet. Diabetes 53: 1949–1952PubMedGoogle Scholar
  55. 55.
    Adams SH, Lei C, Jodka CM et al (2006) PYY[3–36] administration decreases the respiratory quotient and reduces adiposity in diet- induced obese mice. J Nutr 136: 195–201PubMedGoogle Scholar
  56. 56.
    Batterham RL, Cohen MA, Ellis SM et al (2003) Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 349: 941–948PubMedGoogle Scholar
  57. 57.
    Misra M, Prabhakaran R, Miller KK et al (2008) Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II. J Clin Endocrinol Metab 93: 1292–1297PubMedGoogle Scholar
  58. 58.
    Misra M, Miller KK, Cord J et al (2007) Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. J Clin Endocrinol Metab 92: 2046–2052PubMedGoogle Scholar
  59. 59.
    Siahanidou T, Mandyla H, Militsi H et al (2007) Peptide YY (3–36) represents a high percentage of total PYY immunoreactivity in preterm and full-term infants and correlates independently with markers of adiposity and serum ghrelin concentrations. Pediatr Res 62: 200–203PubMedGoogle Scholar
  60. 60.
    Siahanidou T, Mandyla H, Vounatsou M et al (2005) Circulating peptide YY concentrations are higher in preterm than full-term infants and correlate negatively with body weight and positively with serum ghrelin concentrations. Clin Chem 51: 2131–2137PubMedGoogle Scholar
  61. 61.
    Berseth CL, Nordyke CK, Valdes MG et al (1992) Responses of gastrointestinal peptides and motor activity to milk and water feedings in preterm and term infants. Pediatr Res 31: 587–590PubMedGoogle Scholar
  62. 62.
    Sharman-Koendjbiharie M, Hopman WP, Piena-Spoel M et al (2002) Gut hormones in preterm infants with necrotizing enterocolitis during starvation and reintroduction of enteral nutrition. J Pediatr Gastroenterol Nutr 35: 674–679PubMedGoogle Scholar
  63. 63.
    Adrian TE, Smith HA, Calvert SA et al (1986) Elevated plasma peptide YY in human neonates and infants. Pediatr Res 20: 1225–1227PubMedGoogle Scholar
  64. 64.
    van der Lely AJ, Tschop M, Heiman ML, Ghigo E (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25: 426–457PubMedGoogle Scholar
  65. 65.
    Kojima M, Kangawa K (2005) Ghrelin: structure and function. Physiol Rev 85: 495–522PubMedGoogle Scholar
  66. 66.
    Ghigo E, Arvat E, Giordano R et al (2001) Biologic activities of growth hormone secretagogues in humans. Endocrine 14: 87–93PubMedGoogle Scholar
  67. 67.
    Gauna C, Delhanty PJ, Hofland LJ et al (2005) Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 90: 1055–1060PubMedGoogle Scholar
  68. 68.
    Wiedmer P Nogueiras R, Broglio F et al (2007) Ghrelin, obesity and diabetes. Nat Clin Pract Endocrinol Metab 3: 705–712PubMedGoogle Scholar
  69. 69.
    Broglio F, Gottero C, Prodam F et al (2004) Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 89: 3062–3065PubMedGoogle Scholar
  70. 70.
    Gil-Campos M, Aguilera CM, Canete R, Gil A (2006) Ghrelin: a hormone regulating food intake and energy homeostasis. Br J Nutr 96: 201–226PubMedGoogle Scholar
  71. 71.
    Yang J, Brown MS, Liang G et al (2008) Identification of the acyl- transferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132: 387–396PubMedGoogle Scholar
  72. 72.
    Choi K, Roh SG, Hong YH et al (2003) The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis. En¬docrinology 144: 754 - 759Google Scholar
  73. 73.
    Wortley KE, del Rincon JP, Murray JD et al (2005) Absence of ghrelin protects against early-onset obesity. J Clin Invest 115: 3573–3578PubMedGoogle Scholar
  74. 74.
    Wortley KE, Anderson KD, Garcia K et al (2004) Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci 101: 8227–8232PubMedGoogle Scholar
  75. 75.
    Thompson NM, Gill DA, Davies R et al (2004) Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145: 234–242PubMedGoogle Scholar
  76. 76.
    Zhang W, Zhao L, Lin TR et al (2004) Inhibition of adipogenesis by ghrelin. Mol Biol Cell 15: 2484–2491PubMedGoogle Scholar
  77. 77.
    Paik KH, Choe YH, Park WH et al (2006) Suppression of acylated ghrelin during oral glucose tolerance test is correlated with whole- body insulin sensitivity in children with Prader-Willi syndrome. J Clin Endocrinol Metab 91: 1876–1881PubMedGoogle Scholar
  78. 78.
    Leite-Moreira AF, Soares JB (2007) Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov Today 12: 276–288PubMedGoogle Scholar
  79. 79.
    Cummings DE, Weigle DS, Frayo RS et al (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346: 1623–1630PubMedGoogle Scholar
  80. 80.
    Barazzoni R, Zanetti M, Ferreira C et al (2007) Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome. J Clin Endocrinol Metab 92: 3935–3940PubMedGoogle Scholar
  81. 81.
    Zwirska-Korczala K, Adamczyk-Sowa M, Sowa P et al (2007) Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism. J Physiol Pharmacol 58 (Suppl 1): 53–64Google Scholar
  82. 82.
    Gualillo O, Caminos J, Blanco M et al (2001) Ghrelin, a novel pla- cental-derived hormone. Endocrinology 142: 788–794PubMedGoogle Scholar
  83. 83.
    Cortelazzi D, Cappiello V, Morpurgo PS et al (2003) Circulating levels of ghrelin in human fetuses. Eur J Endocrinol 149: 111–116PubMedGoogle Scholar
  84. 84.
    Chanoine JP, Yeung LP, Wong AC, Birmingham CL (2002) Immunoreactive ghrelin in human cord blood: relation to anthropometry, leptin, and growth hormone. J Pediatr Gastroenterol Nutr 35: 282–286PubMedGoogle Scholar
  85. 85.
    Bellone S, Rapa A, Vivenza D et al (2004) Circulating ghrelin levels in the newborn are positively associated with gestational age. Clin Endocrinol 60: 613–617Google Scholar
  86. 86.
    Soriano-Guillen L, Barrios V, Chowen JA et al (2004) Ghrelin levels from fetal life through early adulthood: relationship with endocrine and metabolic and anthropometric measures. J Pediatr 144: 30–35PubMedGoogle Scholar
  87. 87.
    Baldelli R, Bellone S, Castellino N et al (2006) Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children. Clin Endocrinol 64: 255–259Google Scholar
  88. 88.
    Prodam F, Me E, Riganti F et al (2006) The nutritional control of ghrelin secretion in humans: the effects of enteral vs. parenteral nutrition. Eur J Nutr 45: 399–405PubMedGoogle Scholar
  89. 89.
    Nakahara T, Harada T, Yasuhara D et al (2008) Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa. Biol Psychiatry 64: 252–255PubMedGoogle Scholar
  90. 90.
    Whatmore AJ, Hall CM, Jones J et al (2003) Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol 59: 649–654Google Scholar
  91. 91.
    Bideci A, Camurdan MO, Yesilkaya E et al (2008) Serum ghrelin, leptin and resistin levels in adolescent girls with polycystic ovary syndrome. J Obstet Gynaecol Res 34: 578–584PubMedGoogle Scholar
  92. 92.
    Kasa-Vubu JZ, Rosenthal A, Murdock EG, Welch KB (2007) Impact of fatness, fitness, and ethnicity on the relationship of nocturnal ghrelin to 24-hour luteinizing hormone concentrations in adolescent girls. J Clin Endocrinol Metab 92: 3246–3252PubMedGoogle Scholar
  93. 93.
    Pomerants T, Tillmann V, Jurimae J, Jurimae T (2006) Relationship between ghrelin and anthropometrical, body composition parameters and testosterone levels in boys at different stages of puberty. J Endocrinol Invest 29: 962–967PubMedGoogle Scholar
  94. 94.
    Bellone S, Baldelli R, Radetti G et al (2006) Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake. J Clin Endocrinol Metab 91: 1929–1933PubMedGoogle Scholar
  95. 95.
    Bunt JC, Salbe AD, Tschop MH et al (2003) Cross-sectional and prospective relationships of fasting plasma ghrelin concentrations with anthropometric measures in pima Indian children. J Clin Endocrinol Metab 88: 3756–3761PubMedGoogle Scholar
  96. 96.
    James RJ, Drewett RF, Cheetham TD (2004) Low cord ghrelin levels in term infants are associated with slow weight gain over the first 3 months of life. J Clin Endocrinol Metab 89: 3847–3850PubMedGoogle Scholar
  97. 97.
    Savino F, Fissore MF, Grassino EC et al (2005) Ghrelin, leptin and IGF-I levels in breast-fed and formula-fed infants in the first years of life. Acta Paediatr 94: 531–537PubMedGoogle Scholar
  98. 98.
    Chiesa C, Osborn JF, Haass C et al (2008) Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry? Clin Chem 54: 550–558PubMedGoogle Scholar
  99. 99.
    Lanyi E, Varnagy A, Kovacs KA et al (2008) Ghrelin and acyl ghrelin in preterm infants and maternal blood: relationship with endocrine and anthropometric measures. Eur J Endocrinol 158: 27–33PubMedGoogle Scholar
  100. 100.
    Hubler A, Rippel C, Kauf E et al (2006) Associations between ghrelin levels in serum of preterm infants and enteral nutritional state during the first 6 months after birth. Clin Endocrinol 65: 611–616Google Scholar
  101. 101.
    Savino F, Grassino EC, Fissore MF et al (2006) Ghrelin, motilin, insulin concentration in healthy infants in the first months of life: relation to fasting time and anthropometry. Clin Endocrinol 65: 158–162Google Scholar
  102. 102.
    Kalies H, Heinrich J, Borte N et al (2005) The effect of breastfeeding on weight gain in infants: results of a birth cohort study. Eur J Med Res 10: 36–42PubMedGoogle Scholar
  103. 103.
    Ilcol YO, Hizli B (2007) Active and total ghrelin concentrations increase in breast milk during lactation. Acta Paediatr 96: 1632–1639PubMedGoogle Scholar
  104. 104.
    Yokota I, Kitamura S, Hosoda H et al (2005) Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation. Endocr J 52: 271–276PubMedGoogle Scholar
  105. 105.
    Shimizu T, Kitamura T, Yoshikawa N et al (2007) Plasma levels of active ghrelin until 8 weeks after birth in preterm infants: relationship with anthropometric and biochemical measures. Arch Dis Child Fetal Neonatal Ed 92: F291–F292PubMedGoogle Scholar
  106. 106.
    Holst B, Egerod KL, Schild E et al (2007) GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 148: 13–20PubMedGoogle Scholar
  107. 107.
    Tang SQ, Jiang QY, Zhang YL et al (2008) Obestatin: its physico-chemical characteristics and physiological functions. Peptides 29: 639–645PubMedGoogle Scholar
  108. 108.
    Gourcerol G, St-Pierre DH, Tache Y (2007) Lack of obestatin effects on food intake: should obestatin be renamed ghrelin-associ- ated peptide (GAP)? Regul Pept 141: 1–7PubMedGoogle Scholar
  109. 109.
    Zhang JV, Ren PG, vsian-Kretchmer O et al (2005) Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 310: 996–999PubMedGoogle Scholar
  110. 110.
    Qader SS, Hakanson R, Rehfeld JF et al (2008) Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas. Regul Pept 146: 230–237PubMedGoogle Scholar
  111. 111.
    Harada T, Nakahara T, Yasuhara D et al (2008) Obestatin, acyl ghrelin, and des-acyl ghrelin responses to an oral glucose tolerance test in the restricting type of anorexia nervosa. Biol Psychiatry 63: 245–247PubMedGoogle Scholar
  112. 112.
    Zou CC, Liang L, Wang CL, Fu JF, Zhao ZY (2009) The change in ghrelin and obestatin levels in obese children after weight reduction. Acta Paediatr 98: 159–165PubMedGoogle Scholar
  113. 113.
    Poitras P, Peeters TL (2008) Motilin. Curr Opin Endocrinol Dia-betes Obes 15: 54–57Google Scholar
  114. 114.
    Itoh Z (1997) Motilin and clinical application. Peptides 18: 593–608PubMedGoogle Scholar
  115. 115.
    Nishikubo T, Yamakawa A, Kamitsuji H et al (2005) Identification of the motilin cells in duodenal epithelium of premature infants. Pediatr Int 47: 248–251PubMedGoogle Scholar
  116. 116.
    Tomasetto C, Karam SM, Ribieras S et al (2000) Identification and characterization of a novel gastric peptide hormone: the motilin- related peptide. Gastroenterology 119: 395–405PubMedGoogle Scholar
  117. 117.
    Wierup N, Bjorkqvist M, Westrom B et al (2007) Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine. J Clin Endocrinol Metab 92: 3573–3581PubMedGoogle Scholar
  118. 118.
    Bryant MG, Buchan AM, Gregor M et al (1982) Development of intestinal regulatory peptides in the human fetus. Gastroenterology 83: 47–54PubMedGoogle Scholar
  119. 119.
    Janik JS, Track NS, Filler RM (1982) Motilin, human pancreatic polypeptide, gastrin, and insulin plasma concentrations in fasted children. J Pediatr 101: 51–56PubMedGoogle Scholar
  120. 120.
    Mahmoud EL, Benirschke K, Vaucher YE, Poitras P (1988) Motilin levels in term neonates who have passed meconium prior to birth. J Pediatr Gastroenterol Nutr 7: 95–99PubMedGoogle Scholar
  121. 121.
    Shulman DI, Kanarek K (1993) Gastrin, motilin, insulin, and in-sulin-like growth factor-I concentrations in very-low-birth-weight infants receiving enteral or parenteral nutrition. JPEN J Parenter Enteral Nutr 17: 130–133PubMedGoogle Scholar
  122. 122.
    De Clercq P, Springer S, Depoortere I, Peeters TL (1998) Motilin in human milk: identification and stability during digestion. Life Sci 63: 1993–2000PubMedGoogle Scholar
  123. 123.
    Lothe L, Ivarsson SA, Lindberg T (1987) Motilin, vasoactive intestinal peptide and gastrin in infantile colic. Acta Paediatr Scand 76: 316–320PubMedGoogle Scholar
  124. 124.
    Savino F, Grassino EC, Guidi C et al (2006) Ghrelin and motilin concentration in colicky infants. Acta Paediatr 95: 738–741PubMedGoogle Scholar
  125. 125.
    Gibbs J, Young RC, Smith GP (1973) Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 84: 488–495PubMedGoogle Scholar
  126. 126.
    Moran TH (2000) Cholecystokinin and satiety: current perspectives. Nutrition 16: 858–865PubMedGoogle Scholar
  127. 127.
    Woods SC (2004) Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake. Am J Physiol Gastrointest Liver Physiol 286: G7–G13PubMedGoogle Scholar
  128. 128.
    West DB, Greenwood MR, Marshall KA, Woods SC (1987) Lithium chloride, cholecystokinin and meal patterns: evidence that chole- cystokinin suppresses meal size in rats without causing malaise. Appetite 8: 221–227PubMedGoogle Scholar
  129. 129.
    Covasa M, Marcuson JK, Ritter RC (2001) Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin. Am J Physiol Regul Integr Comp Physiol 280: R331–R337PubMedGoogle Scholar
  130. 130.
    Uvnas-Moberg K, Marchini G, Winberg J (1993) Plasma cholecys- tokinin concentrations after breast feeding in healthy 4 day old infants. Arch Dis Child 68: 46–48PubMedGoogle Scholar
  131. 131.
    Marchini G, Linden A (1992) Cholecystokinin, a satiety signal in newborn infants? J Dev Physiol 17: 215–219PubMedGoogle Scholar
  132. 132.
    Tornhage CJ, Serenius F, Uvnas-Moberg K, Lindberg T (1995) Plasma somatostatin and cholecystokinin levels in preterm infants and their mothers at birth. Pediatr Res 37: 771–776PubMedGoogle Scholar
  133. 133.
    Tornhage CJ, Serenius F, Uvnas-Moberg K, Lindberg T (1996) Plasma somatostatin and cholecystokinin levels in preterm infants during the first day of life. Biol Neonate 70: 311–321PubMedGoogle Scholar
  134. 134.
    Tornhage CJ, Serenius F, Uvnas-Moberg K, Lindberg T (1998) Plasma somatostatin and cholecystokinin levels in preterm infants during kangaroo care with and without nasogastric tube-feeding. J Pediatr Endocrinol Metab 11: 645–651PubMedGoogle Scholar
  135. 135.
    Teitelbaum DH, Han-Markey T, Drongowski RA et al (1997) Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr 21: 100–103PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Flavia Prodam
  • Simonetta Bellone
  • Silvia Savastio
  • Arianna Busti
  • Carla Guidi
  • Alice Monzani
  • Gianni Bona
    • 1
  1. 1.Department of Medical Science, Division of PediatricsUniversity of Piemonte OrientaleNovaraItaly

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