Download PDF
Horm Metab Res 2011; 43(8): 580-586
DOI: 10.1055/s-0031-1279779
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Growth Hormone, Ghrelin and Peptide YY Secretion after Oral Glucose Administration in Healthy and Obese Women

E. Outeiriño-Blanco1 , J. Garcia-Buela2 , S. Sangiao-Alvarellos3 , 4 , S. Pertega-Diaz5 , T. Martinez-Ramonde1 , F. Cordido1 , 3 , 4
  • 1Department of Endocrinology, University Hospital A Coruña, A Coruña, Spain
  • 2Department of Laboratory, University Hospital A Coruña, A Coruña, Spain
  • 3Department of Investigation, University Hospital A Coruña, A Coruña, Spain
  • 4Department of Medicine, University of A Coruña, A Coruña, Spain
  • 5Clinical Epidemiology and Biostatistics Unit, University Hospital A Coruña, A Coruña, Spain
Further Information

Publication History

received 25.01.2011

accepted 12.05.2011

Publication Date:
10 June 2011 (online)

Also available at
    Permissions and Reprints

Abstract

The mechanism of the altered GH secretion in obesity is unclear. There is evidence that oral glucose (OG) administration initially decreases and subsequently stimulates GH secretion. Ghrelin is a peptide that displays strong growth hormone-releasing activity. Its physiological importance on GH regulation is unclear. Our aim was to study fasting GH concentrations and their response to OG administration in relation with ghrelin secretion in obese and healthy women, in order to elucidate the hypothetical participation of ghrelin on post-oral glucose GH secretion. 36 women were included in the study. After an overnight fast, 75 g of oral glucose was administered; glucose, insulin, ghrelin, and PYY1–36 were obtained at baseline and during 300 min. The area under the curve between 0 and 300 min (AUC) of GH μ/l·min) was lower in obese patients than in controls; 262.5±57.5 vs. 534.9±95.6, p=0.01, for obese and controls respectively. GH peak (μg/l) was lower in obese patients than in controls; 3.7±0.7 vs. 7.1±1.0, p=0.012, for obese and controls, respectively. The AUC of total ghrelin (pg/ml·min) was lower in obese patients than in controls; 233 032±12 641 vs. 333 697±29 877, p=0.004, for the obese patients and controls respectively. PYY1–36 was similar in obese and healthy women after OG. There were significant correlations between the different indices of post-oral glucose GH and ghrelin secretion. These data suggest that ghrelin is a physiological regulator of GH in the post-oral glucose state, and the decreased ghrelin secretion could be one of the mechanisms responsible for the altered GH secretion in obesity.

Key words

GH - oral glucose - women - obesity - ghrelin

References

  • 1 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach.  Nature. 1999;  402 656-660
    Google Scholar
  • 2 Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LH. A receptor in pituitary and hypothalamus that functions in growth hormone release.  Science. 1996;  273 974-977
    Google Scholar
  • 3 Cordido F, Penalva A, Dieguez C, Casanueva FF. Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity.  J Clin Endocrinol Metab. 1993;  76 819-823
    Google Scholar
  • 4 Alvarez-Castro P, Isidro ML, Garcia-Buela J, Leal-Cerro A, Broglio F, Tassone F, Ghigo E, Dieguez C, Casanueva FF, Cordido F. Marked GH secretion after ghrelin alone or combined with GH-releasing hormone (GHRH) in obese patients.  Clin Endocrinol (Oxf). 2004;  61 250-255
    Google Scholar
  • 5 Alaioubi B, Mann K, Petersenn S. Diagnosis of growth hormone deficiency in adults: provocative testing with GHRP6 in comparison to the insulin tolerance test.  Horm Metab Res. 2009;  41 238-243
    Google Scholar
  • 6 Lanfranco F, Motta G, Baldi M, Gasco V, Grottoli S, Benso A, Broglio F, Ghigo E. Ghrelin and anterior pituitary function.  Front Horm Res. 2010;  38 206-211
    Google Scholar
  • 7 Espelund U, Hansen TK, Højlund K, Beck-Nielsen H, Clausen JT, Hansen BS, Orskov H, Jørgensen JO, Frystyk J. Fasting unmasks a strong inverse association between ghrelin and cortisol in serum: studies in obese and normal-weight subjects.  J Clin Endocrinol Metab. 2005;  90 741-746
    Google Scholar
  • 8 Norrelund H. The metabolic role of growth hormone in humans with particular reference to fasting.  Growth Horm IGF Res. 2005;  15 95-122
    Google Scholar
  • 9 Natalucci G, Riedl S, Gleiss A, Zidek T, Frisch H. Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern.  Eur J Endocrinol. 2005;  152 845-850
    Google Scholar
  • 10 Avram AM, Jaffe CA, Symons KV, Barkan AL. Endogenous circulating ghrelin does not mediate growth hormone rhythmicity or response to fasting.  J Clin Endocrinol Metab. 2005;  90 2982-2987
    Google Scholar
  • 11 Dall R, Kanaley J, Hansen TK, Møller N, Christiansen JS, Hosoda H, Kangawa K, Jørgensen JO. Plasma ghrelin levels during exercise in healthy subjects and in growth hormone-deficient patients.  Eur J Endocrinol. 2002;  147 65-70
    Google Scholar
  • 12 Pérez-Fontán M, Cordido F, Rodríguez-Carmona A, García-Naveiro R, Isidro ML, Villaverde P, García-Buela J. Acute plasma ghrelin and leptin responses to oral feeding or intraperitoneal hypertonic glucose-based dialysate in patients with chronic renal failure.  Kidney Int. 2005;  68 2877-2885
    Google Scholar
  • 13 Isidro ML, Nemina R, Garcia-Buela J, Sangiao-Alvarellos S, Cordido F. Effect of oral glucose on acylated and total ghrelin secretion in acromegalic patients.  Neuro Endocrinol Lett. 2007;  28 596-603
    Google Scholar
  • 14 Muller AF, Lamberts SW, Janssen JA, Hofland LJ, Koetsveld PV, Bidlingmaier M, Strasburger CJ, Ghigo E, Van der Lely AJ. Ghrelin drives GH secretion during fasting in man.  Eur J Endocrinol. 2002;  146 203-207
    Google Scholar
  • 15 Koutkia P, Schurgin S, Berry J, Breu J, Lee BS, Klibanski A, Grinspoon S. Reciprocal changes in endogenous ghrelin and growth hormone during fasting in healthy women.  Am J Physiol Endocrinol Metab. 2005;  289 E814-E822
    Google Scholar
  • 16 Misra M, Miller KK, Kuo K, Griffin K, Stewart V, Hunter E, Herzog DB, Klibanski A. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents.  Am J Physiol Endocrinol Metab. 2005;  289 E347-E356
    Google Scholar
  • 17 Nass R, Farhy LS, Liu J, Prudom CE, Johnson ML, Veldhuis P, Pezzoli SS, Oliveri MC, Gaylinn BD, Geysen HM, Thorner MO. Evidence for acyl-ghrelin modulation of growth hormone release in the fed state.  J Clin Endocrinol Metab. 2008;  93 1988-1994
    Google Scholar
  • 18 Lloyd B, Ravi P, Mendes N, Klibanski A, Misra M. Peptide YY levels across pubertal stages and associations with growth hormone.  J Clin Endocrinol Metab. 2010;  95 2957-2962
    Google Scholar
  • 19 Cordido F, Casanueva FF, Dieguez C. Cholinergic receptor activation by pyridostigmine restores growth hormone (GH) responsiveness to GH-releasing hormone administration in obese subjects: evidence for hypothalamic somatostatinergic participation in the blunted GH release of obesity.  J Clin Endocrinol Metab. 1989;  68 290-293
    Google Scholar
  • 20 Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, Hilsted J, Skakkebae NE. Massive weight loss restores 24-h growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects.  J Clin Endocrinol Metab. 1995;  80 1407-1415
    Google Scholar
  • 21 Kelijman M, Frohman LA. Enhanced growth hormone (GH) responsiveness to GH-releasing hormone after dietary manipulation in obese and nonobese subjects.  J Clin Endocrinol Metab. 1988;  66 489-494
    Google Scholar
  • 22 Furuhata Y, Kagaya R, Hirabayashi K, Ikeda A, Chang KT, Nishihara M, Takahashi M. Development of obesity in transgenic rats with low circulating growth hormone levels: involvement of leptin resistance.  Eur J Endocrinol. 2000;  143 535-541
    Google Scholar
  • 23 Mekala KC, Tritos NA. Effects of Recombinant Human Growth Hormone Therapy in Obesity in Adults – a Meta-Analysis.  J Clin Endocrinol Metab. 2009;  94 130-137
    Google Scholar
  • 24 Valcavi R, Zini M, Volta C, Ghizzoni L, Azzarito C, Bernasconi S, Portioli I. Effects of oral glucose administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH release in children and adults.  J Clin Endocrinol Metab. 1994;  79 1152-1157
    Google Scholar
  • 25 Grottoli S, Procopio M, Maccario M, Zini M, Oleandri SE, Tassone F, Valcavi R, Ghigo E. In obesity, glucose load loses its early inhibitory, but maintains its late stimulatory, effect on somatotrope secretion.  J Clin Endocrinol Metab. 1997;  82 2261-2265
    Google Scholar
  • 26 Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion.  J Clin Endocrinol Metab. 2002;  87 240-244
    Google Scholar
  • 27 Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans.  Diabetes. 2001;  50 1714-1719
    Google Scholar
  • 28 Kojima M, Kangawa K. Ghrelin: structure and function.  Physiol Rev. 2005;  85 495-522
    Google Scholar
  • 29 Benedini S, Codella R, Caumo A, Marangoni F, Luzi L. Different circulating ghrelin responses to isoglucidic snack food in healthy individuals.  Horm Metab Res. 2011;  43 135-140
    Google Scholar
  • 30 Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.  N Engl J Med. 2002;  346 1623-1630
    Google Scholar
  • 31 Karra E, Batterham RL. The role of gut hormones in the regulation of body weight and energy homeostasis.  Mol Cell Endocrinol. 2010;  316 120-128
    Google Scholar
  • 32 Cordido F, Garcia-Buela J, Sangiao-Alvarellos S, Martinez T, Vidal O. The decreased growth hormone response to growth hormone releasing hormone in obesity is associated to cardiometabolic risk factors.  Mediators Inflamm. 2010;  2010 434–562
    Google Scholar
  • 33 van der Lely AJ, Tschop M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin.  Endocr Rev. 2004;  25 426-457
    Google Scholar
  • 34 Osterstock G, Escobar P, Mitutsova V, Gouty-Colomer LA, Fontanaud P, Molino F, Fehrentz JA, Carmignac D, Martinez J, Guerineau NC, Robinson IC, Mollard P, Méry PF. Ghrelin stimulation of growth hormone-releasing hormone neurons is direct in the arcuate nucleus.  PLoS ONE. 2010;  5 e9159
    Google Scholar
  • 35 Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell Jr FE, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.  Ann Intern Med. 2008;  149 601-611
    Google Scholar
  • 36 Zizzari P, Halem H, Taylor J, Dong JZ, Datta R, Culler MD, Epelbaum J, Bluet-Pajot MT. Endogenous ghrelin regulates episodic growth hormone (GH) secretion by amplifying GH Pulse amplitude: evidence from antagonism of the GH secretagogue-R1a receptor.  Endocrinology. 2005;  146 3836-3842
    Google Scholar
  • 37 Pantel J, Legendre M, Nivot S, Morisset S, Vie-Luton MP, le Bouc Y, Epelbaum J, Amselem S. Recessive isolated growth hormone deficiency and mutations in the ghrelin receptor.  J Clin Endocrinol Metab. 2009;  94 4334-4341
    Google Scholar
  • 38 Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor.  P Natl Acad Sci USA. 2004;  101 4679-4684
    Google Scholar
  • 39 Zhao TJ, Liang G, Li RL, Xie X, Sleeman MW, Murphy AJ, Valenzuela DM, Yancopoulos GD, Goldstein JL, Brown MS. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice.  P Natl Acad Sci USA. 2010;  107 7467-7472
    Google Scholar
  • 40 Broglio F, Benso A, Gottero C, Prodam F, Grottoli S, Tassone F, Maccario M, Casanueva FF, Dieguez C, Deghenghi R, Ghigo E, Arvat E. Effects of glucose, free fatty acids or arginine load on the GH-releasing activity of ghrelin in humans.  Clin Endocrinol (Oxf). 2002;  57 265-271
    Google Scholar
  • 41 Cordido F, Fernandez T, Martinez T, Peñalva A, Peinó R, Casanueva FF, Dieguez C. Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism.  J Clin Endocrinol Metab. 1998;  83 4350-4354
    Google Scholar
  • 42 Vestergaard ET, Dall R, Lange KH, Kjaer M, Christiansen JS, Jorgensen JO. The ghrelin response to exercise before and after growth hormone administration.  J Clin Endocrinol Metab. 2007;  92 297-303
    Google Scholar
  • 43 Gormsen LC, Nielsen C, Gjedsted J, Gjedde S, Vestergaard ET, Christiansen JS, Jørgensen JO, Møller N. Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans.  Clin Endocrinol (Oxf). 2007;  66 641-645
    Google Scholar
  • 44 Yamashita S, Melmed S. Insulin regulation of rat growth hormone gene transcription.  J Clin Invest. 1986;  78 1008-1014
    Google Scholar
  • 45 Clasey JL, Weltman A, Patrie J, Weltman JY, Pezzoli S, Bouchard C, Thorner MO, Hartman ML. Abdominal visceral fat and fasting insulin are important predictors of 24-h GH release independent of age, gender, and other physiological factors.  J Clin Endocrinol Metab. 2001;  86 3845-3852
    Google Scholar
  • 46 Haqq AM, Farooqi IS, O’Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, LaFranchi SH, Purnell JQ. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome.  J Clin Endocrinol Metab. 2003;  88 174-178
    Google Scholar
  • 47 McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls.  J Clin Endocrinol Metab. 2004;  89 1630-1635
    Google Scholar
  • 48 Hotta M, Ohwada R, Katakami H, Shibasaki T, Hizuka N, Takano K. Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa.  J Clin Endocrinol Metab. 2004;  89 5707-5712
    Google Scholar
  • 49 Blatnik M, Soderstrom CI. A practical guide for the stabilization of acylghrelin in human blood collections.  Clin Endocrinol (Oxf). 2011;  74 325-331
    Google Scholar
  • 50 Tassone F, Broglio F, Destefanis S, Rovere S, Benso A, Gottero C, Prodam F, Rossetto R, Gauna C, van der Lely AJ, Ghigo E, Maccario M. Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity.  J Clin Endocrinol Metab. 2003;  88 5478-5483
    Google Scholar
  • 51 Johannsson G. Central adiposity as an important confounder in the diagnosis of adult growth hormone deficiency.  J Clin Endocrinol Metab. 2008;  93 4221-4223
    Google Scholar
  • 52 De Marinis L, Bianchi A, Mancini A, Gentilella R, Perrelli M, Giampietro A, Porcelli T, Tilaro L, Fusco A, Valle D, Tacchino RM. Growth hormone secretion and leptin in morbid obesity before and after biliopancreatic diversion: relationships with insulin and body composition.  J Clin Endocrinol Metab. 2004;  89 174-180
    Google Scholar
  • 53 Makimura H, Stanley T, Mun D, You SM, Grinspoon S. The effects of central adiposity on growth hormone (GH) response to GH-releasing hormone-arginine stimulation testing in men.  J Clin Endocrinol Metab. 2008;  93 4254-4260
    Google Scholar
  • 54 Rasmussen MH, Juul A, Hilsted J. Effect of weight loss on free insulin-like growth factor-I in obese women with hyposomatotropism.  Obesity (Silver Spring). 2007;  15 879-886
    Google Scholar

Correspondence

F. CordidoMD 

Servicio de Endocrinología

University Hospital A Coruña

Xubias de Arriba 84

15006 La Coruña

Spain

Phone: +34/98/117 8000

Fax: +34/98/117 8204

Email: Fernando.Cordido.Carballido@sergas.es

      >