Division of Endocrinology and Metabolism, Department of Internal Medicine (F.B., E.A., A.B., C.G., E.G.); Department of Anatomy, Pharmacology and Forensic Medicine (G.M.); Department of Biomedical Sciences and Oncology (M.P.); University of Turin, Italy; Division of Endocrinology, Department of Internal Medicine, Erasmus University of Rotterdam (A.J.V.D.L.), The Netherlands; and Europeptides (R.D.), Argenteuil, France
Abstract
Ghrelin, a 28 amino acid gastric hormone is a natural ligand of the
GH Secretagogue (GHS) receptor (GHS-R) and strongly stimulates GH
secretion though, like synthetic GHS, it shows other endocrine and
non-endocrine activities. Aim of the present study was to clarify
whether ghrelin administration influences insulin and glucose levels in
humans. To this goal, we compared the effects of ghrelin, hexarelin, a
synthetic GHS, or placebo on insulin and glucose as well as on GH
levels in 11 normal young volunteers (age [mean ± SEM]: 28.5 ± 3.1
yr; BMI: 22.2 ± 0.9 Kg/m2). Ghrelin induced very marked
increase in GH secretion (AUC0180: 5777.1 ± 812.6
µg/l/h; p < 0.01) which was not modified by placebo. Placebo
administration did not modify insulin and glucose levels. On the other
hand, ghrelin administration induced a prompt increase in glucose
levels (
AUC0-180: 1343.1 ± 443.5 mg/dl/h; p < 0.01 vs.
saline). Absolute glucose levels at +15' were already higher than those
at baseline (93.9 ± 7.1 mg/dl; p < 0.01) and persisted elevated up to
165' (90.3 ± 5.8 mg/dl; p < 0.01 vs. 0'). Ghrelin administration was
also followed by a decrease in serum insulin levels
(
AUC0-180: -207.1 ± 70.5 mU/l/h; p < 0.05 vs.
saline). Absolute insulin levels were significantly reduced from 30'
(11.4 ± 0.9 mU/l, p < 0.1 vs. 0'), showed the nadir at +45' (10.0 ±
0.6 mU/l, p < 0.01 vs. 0') and then persisted lower (p < 0.01) than
baseline up to +105'. Hexarelin administration did not modify glucose
and insulin levels despite its marked GH-releasing effect
(
AUC0-180: 4156.8 ± 1180.3 µg/l/h; p < 0.01 vs.
saline) that was slightly lower (p < 0.05) than that of ghrelin. In
conclusion, these findings show that, besides stimulating GH secretion,
ghrelin is a gastric hormone possessing metabolic actions such as
hyperglycemic effect and lowering effect on insulin secretion in
humans, at least after acute administration.