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/m(2)).
Ghrelin induced very marked increase in GH secretion (DeltaAUC(0-180): 5777.1 +/- 812.6 microg/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 (DeltaAUC(0-180): 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 (DeltaAUC(0-180): -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 (DeltaAUC(0-180): 4156.8 +/- 1180.3 microg/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.