title: Effects of glucose, free fatty acids or arginine load on the GH-releasing activity of ghrelin in humans.
abstract: OBJECTIVE
  Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an n-octanoyl ester in serine-3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R) and strongly stimulates GH secretion. In humans, ghrelin is more potent than growth hormone-releasing hormone (GHRH) and non-natural GHS such as hexarelin. Moreover, ghrelin shows a true synergism with GHRH, has no interaction with hexarelin and, similarly to non-natural GHS, is partially refractory to the inhibitory effect of exogenous somatostatin (SS). Despite this evidence, the mechanisms underlying the GH-releasing effect of ghrelin in humans have not been fully clarified.
  
  
  METHODS
  To this aim we enrolled six normal young volunteers [age (mean +/- SEM) 28.9 +/- 3.1 year; body mass index 22.3 +/- 1.0 kg/m2).
  
  
  METHODS
  In all subjects we studied the effects of glucose (OGTT, 100 g oral glucose at -45 min) or free fatty acids (FFA) load [lipid-heparin emulsion, Li-He, Intralipid 10% 250 ml + heparin 2500 U i.v. from -30 to +120 min] as well as of arginine (ARG, 0.5 g/kg infused from 0 to +30 min) on the GH response to human ghrelin (1.0 micro g/kg i.v. at 0 min) administration. These results were compared with those obtained by studying the effects of OGTT, Li-He and ARG on the GH response to GHRH-29 (1.0 micro g/kg i.v. at 0 min).
  
  
  RESULTS
  The GH response to ghrelin (auc 5452.4 +/- 991.3 micro g/l/h) was higher (P < 0.05) than that after GHRH (1519.4 +/- 93.3 micro g/l/h). The GH response to GHRH was inhibited by OGTT (450.7 +/- 81.1 micro g/l/h, P < 0.05) and almost abolished by Li-He (230.0 +/- 63.6 micro g/l/h, P < 0.05) while was markedly potentiated by ARG (2520.4 +/- 425.8 micro g/l/h, P < 0.05). The GH response to GHRH + ARG, however, was lower (P < 0.05) than that to ghrelin alone. The GH response to ghrelin was blunted by OGTT (2153.1 +/- 781.9 micro g/l/h, P < 0.05) as well as by Li-He (3158.8 +/- 426.7 micro g/l/h, P < 0.05) but these responses remained higher (P < 0.05) than that to GHRH alone. On the other hand, ARG did not modify the GH response to ghrelin (6324.3 +/- 1275.5 micro g/l/h). For GH 1 micro g/l = 2 mU/l.
  
  
  CONCLUSIONS
  In humans, ghrelin exerts a strong stimulatory effect on GH secretion which is partially refractory to the inhibitory effect of both glucose and FFA load and is not enhanced by ARG. These factors almost abolish and potentiate, respectively, the GH response to GHRH, at least partially, via modulation of hypothalamic SS release. Thus, our findings agree with the hypothesis that ghrelin as well as non-natural GHS acts, at least partially, by antagonizing SS activity.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Broglio
authors.forename: Andrea
authors.initials: A
authors.lastname: Benso
authors.forename: Cristina
authors.initials: C
authors.lastname: Gottero
authors.forename: Flavia
authors.initials: F
authors.lastname: Prodam
authors.forename: Silvia
authors.initials: S
authors.lastname: Grottoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Tassone
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccario
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.forename: Carlos
authors.initials: C
authors.lastname: Dieguez
authors.forename: Romano
authors.initials: R
authors.lastname: Deghenghi
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arvat
mesh_terms: D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D054439:Ghrelin; D005947:Glucose / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D036361:Peptide Hormones; D010455:Peptides; D013268:Stimulation, Chemical
chemical_list: D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D013006:Growth Hormone; D001120:Arginine; D005947:Glucose