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/m2). Ghrelin induced very marked increase in GH secretion (ΔAUC0-180: 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 (ΔAUC0-180: 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 (ΔAUC0-180: -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 (ΔAUC0-180: 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.

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