title: Ghrelin does not mediate the somatotroph and corticotroph responses to the stimulatory effect of glucagon or insulin-induced hypoglycaemia in humans.
abstract: OBJECTIVE
  Acylated ghrelin, a gastric peptide, possesses a potent GH- but also significant ACTH/cortisol-releasing activity mediated by the activation of GH secretagogue receptors (GHS-R) at the hypothalamus-pituitary level. The physiological role of ghrelin in the control of somatotroph and corticotroph function is, however, largely unclear. Glucagon is known to induce a clear increase of GH, ACTH and cortisol levels in humans, at least after intramuscular administration. In fact, glucagon is considered to be a classical alternative to insulin-induced hypoglycaemia (ITT) for the combined evaluation of the function of GH and the hypothalamus-pituitary-adrenal (HPA) axis. We aimed to clarify whether ghrelin mediate the GH and corticotroph responses to intramuscular glucagon or ITT, which has recently been reported able to induce a surprising ghrelin decrease.
  
  
  METHODS
  To this aim we enrolled six normal young male subjects [age (mean +/- SD): 29.0 +/- 8.0 years, body mass index (BMI) 21.9 +/- 2.5 kg/m(2)].
  
  
  METHODS
  In all the subjects we studied ghrelin, GH, ACTH, cortisol and glucose levels after glucagon (GLU; 0.017 mg/kg intramuscularly), ITT (0.1 IU/kg insulin intravenously) or saline administration.
  
  
  RESULTS
  Saline infusion was not followed by any significant variation in ghrelin, GH and glucose levels while ACTH and cortisol showed the expected spontaneous morning trend toward a decrease. GLU administration increased (P < 0.01) circulating GH, ACTH and cortisol as well as insulin and glucose levels. ITT induced an obvious increase (P < 0.01) of GH, ACTH and cortisol levels. The ITT-induced increases in GH and ACTH, but not cortisol, levels were higher (P < 0.01) than those after GLU. Circulating ghrelin levels were not modified by GLU. On the other hand, ghrelin levels underwent a transient reduction (P < 0.01) after insulin-induced hypoglycaemia.
  
  
  CONCLUSIONS
  Ghrelin does not mediate the GH and ACTH responses to glucagon or to the ITT. In fact, ghrelin levels are not modified at all by glucagon and transiently decrease during the ITT. These findings support the assumption that ghrelin does not play a major role in the physiological control of somatotroph and corticotroph function.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Erasmus University of Rotterdam, Rotterdam, The Netherlands.
authors.forename: Fabio
authors.initials: F
authors.lastname: Broglio
authors.forename: Flavia
authors.initials: F
authors.lastname: Prodam
authors.forename: Cristina
authors.initials: C
authors.lastname: Gottero
authors.forename: Silvia
authors.initials: S
authors.lastname: Destefanis
authors.forename: Elisa
authors.initials: E
authors.lastname: Me
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Riganti
authors.forename: Roberta
authors.initials: R
authors.lastname: Giordano
authors.forename: Andreea
authors.initials: A
authors.lastname: Picu
authors.forename: Marcella
authors.initials: M
authors.lastname: Balbo
authors.forename: Aart Jan
authors.initials: AJ
authors.lastname: Van der Lely
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arvat
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D054439:Ghrelin; D005934:Glucagon; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D007328:Insulin; D008297:Male; D036361:Peptide Hormones / Q000097:blood*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone