title: Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans.
abstract: BACKGROUND
  Circulating ghrelin levels are reported to be suppressed by insulin, GH and free fatty acids (FFAs). However, insulin, GH and FFA levels are all interdependent, and it is therefore difficult to delineate their independent effects on ghrelin secretion.
  
  
  OBJECTIVE
  To isolate and define the impact of GH, GH receptor (GHR) blockade and intravenous FFA infusion on total circulating ghrelin levels during a hyperinsulinaemic glucose clamp with identical insulin levels.
  
  
  METHODS
  In a randomized design, eight healthy males each underwent an 8-h hyperinsulinaemic glucose clamp on four occasions together with either: (1) control (saline), (2) intravenous FFA infusion (intralipid/heparin infusion 4 h), (3) a GH bolus (0.5 mg i.v.) or (4) GHR blockade (pegvisomant, 30 mg s.c.).
  
  
  RESULTS
  Hyperinsulinaemia per se resulted in a decrease in ghrelin concentrations of about 15%. During FFA exposure, ghrelin levels were suppressed by about 22% when compared with saline [area under the curve (AUC)(ghrelin0-240) 122.7 +/- 10.9 vs. 97.6 +/- 13.4 pg/ml/min, P = 0.001], followed by a rebound increase upon discontinuation of the infusion. Furthermore, average ghrelin concentration (AUC(ghrelin)) was significantly inversely correlated to average FFA levels (AUC(FFA)) (r = -0.33, P < 0.05). Neither GH administration nor GHR blockade resulted in significant alterations in total ghrelin levels in the presence of unaltered insulin and FFA levels.
  
  
  CONCLUSIONS
  Elevation of FFAs by means of an intravenous infusion acutely suppresses ghrelin levels, whereas GH administration and GHR blockade have no detectable effect on ghrelin concentration when insulin and FFA levels are kept fixed.
authors.affiliation: Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus C, Denmark. lars.christian.gormsen@ki.au.dk
authors.forename: Lars C
authors.initials: LC
authors.lastname: Gormsen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nielsen
authors.forename: Jakob
authors.initials: J
authors.lastname: Gjedsted
authors.forename: Signe
authors.initials: S
authors.lastname: Gjedde
authors.forename: Esben Thyssen
authors.initials: ET
authors.lastname: Vestergaard
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Jens Otto
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D003864:Depression, Chemical; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D054439:Ghrelin; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D036361:Peptide Hormones / Q000097:blood*; D011863:Radioimmunoassay / Q000379:methods; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*
chemical_list: D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013006:Growth Hormone; C406545:pegvisomant