Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans.
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.
Gormsen
Lars C
LC
Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus C, Denmark. lars.christian.gormsen@ki.au.dk
Nielsen
Charlotte
C
Gjedsted
Jakob
J
Gjedde
Signe
S
Vestergaard
Esben Thyssen
ET
Christiansen
Jens S
JS
Jørgensen
Jens Otto
JO
Møller
Niels
N
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*
D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013006:Growth Hormone; C406545:pegvisomant