Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.
OBJECTIVE
The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose-stimulated insulin secretion in healthy subjects.


METHODS
Ghrelin (0.3, 0.9 and 1.5 nmol/kg/h) or saline was infused for more than 65 min in 12 healthy patients (8 male/4 female) on 4 separate occasions in a counterbalanced fashion. An intravenous glucose tolerance test was performed during steady state plasma ghrelin levels. The acute insulin response to intravenous glucose (AIRg) was calculated from plasma insulin concentrations between 2 and 10 min after the glucose bolus. Intravenous glucose tolerance was measured as the glucose disappearance constant (Kg) from 10 to 30 min.


RESULTS
The three ghrelin infusions raised plasma total ghrelin concentrations to 4-, 15-, and 23-fold above the fasting level, respectively. Ghrelin infusion did not alter fasting plasma insulin or glucose, but compared with saline, the 0.3, 0.9, and 1.5 nmol/kg/h doses decreased AIRg (2,152 +/- 448 vs. 1,478 +/- 2,889, 1,419 +/- 275, and 1,120 +/- 174 pmol/l) and Kg (0.3 and 1.5 nmol/kg/h doses only) significantly (P < 0.05 for all). Ghrelin infusion raised plasma growth hormone and serum cortisol concentrations significantly (P < 0.001 for both), but had no effect on glucagon, epinephrine, or norepinephrine levels (P = 0.44, 0.74, and 0.48, respectively).


CONCLUSIONS
This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans. Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve beta-cell function.
Tong
Jenny
J
1Department of Medicine, Division of Endocrinology, University of Cincinnati, Cincinnati, Ohio, USA. jenny.tong@uc.edu
Prigeon
Ronald L
RL
Davis
Harold W
HW
Bidlingmaier
Martin
M
Kahn
Steven E
SE
Cummings
David E
DE
Tschöp
Matthias H
MH
D'Alessio
David
D
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005260:Female; D054439:Ghrelin / Q000494:pharmacology*; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D055815:Young Adult
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D013006:Growth Hormone; D005947:Glucose; D006854:Hydrocortisone