Acute effects of ghrelin administration on glucose and lipid metabolism.
BACKGROUND
Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH.


OBJECTIVE
Our objective was to study direct effects of ghrelin on substrate metabolism.


METHODS
This was a randomized, single-blind, placebo-controlled two-period crossover study.


METHODS
The study was performed in a university clinical research laboratory.


METHODS
Eight healthy men aged 27.2 +/- 0.9 yr with a body mass index of 23.4 +/- 0.5 kg/m(2) were included in the study.


METHODS
Subjects received infusion of ghrelin (5 pmol x kg(-1) x min(-1)) or placebo for 5 h together with a pancreatic clamp (somatostatin 330 microg x h(-1), insulin 0.1 mU x kg(-1) x min(-1), GH 2 ng x kg(-1) x min(-1), and glucagon 0.5 ng.kg(-1) x min(-1)). A hyperinsulinemic (0.6 mU x kg(-1) x min(-1)) euglycemic clamp was performed during the final 2 h of each infusion.


RESULTS
Basal and insulin-stimulated glucose disposal decreased with ghrelin [basal: 1.9 +/- 0.1 (ghrelin) vs. 2.3 +/- 0.1 mg x kg(-1) x min(-1), P = 0.03; clamp: 3.9 +/- 0.6 (ghrelin) vs. 6.1 +/- 0.5 mg x kg(-1) x min(-1), P = 0.02], whereas endogenous glucose production was similar. Glucose infusion rate during the clamp was reduced by ghrelin [4.0 +/- 0.7 (ghrelin) vs. 6.9 +/- 0.9 mg.kg(-1) x min(-1); P = 0.007], whereas nonesterified fatty acid flux increased [131 +/- 26 (ghrelin) vs. 69 +/- 5 micromol/min; P = 0.048] in the basal period. Regional lipolysis (skeletal muscle, sc fat) increased insignificantly with ghrelin infusion. Energy expenditure during the clamp decreased after ghrelin infusion [1539 +/- 28 (ghrelin) vs. 1608 +/- 32 kcal/24 h; P = 0.048], but the respiratory quotient did not differ. Minor but significant elevations in serum levels of GH and cortisol were observed after ghrelin infusion.


CONCLUSIONS
Administration of exogenous ghrelin causes insulin resistance in muscle and stimulates lipolysis; these effects are likely to be direct, although a small contribution of GH and cortisol cannot be excluded.
Vestergaard
Esben Thyssen
ET
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, DK-8000 Aarhus C, Denmark. e.t.vestergaard@ki.au.dk
Djurhuus
Christian Born
CB
Gjedsted
Jakob
J
Nielsen
Søren
S
Møller
Niels
N
Holst
Jens Juul
JJ
Jørgensen
Jens Otto Lunde
JO
Schmitz
Ole
O
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D054439:Ghrelin / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism; D016037:Single-Blind Method
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone