Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans

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 (Delta AUC(0-180): 5777.1 +/- 812.6 mug/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 (AUC(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 (AUC(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< 0.01 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 (Delta AUC(0-180): 4156.8 +/- 1180.3 mug/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.