Glucagon inhibits ghrelin secretion in humans

Objective: It is well known that i.m. glucagon administration stimulates GH and cortisol release in humans, although the mechanisms are unclear. These effects are similar to those described for ghrelin on somatotroph and corticotroph function. The aim of the present study was to investigate the role of ghrelin in mediating the stimulatory effects of glucagon and to evaluate the effect of glucagon on ghrelin secretion. Design and methods: We studied the endocrine and metabolic response to i.m. glucagon administration in 24 subjects (14 men, 10 women; age 19-65 years; body mass index, 25.3±1 kg/m²), who were shown to have an intact anterior pituitary function as evaluated before enclosure. Results: Serum ghrelin concentrations fell significantly at 30, 60, 120 and 180 min after glucagon administration (means±S.E.M.; baseline, 377.9±34.5 pg/ml; nadir, 294.6±28.3 pg/ml (60 min); P < 0.01). Conversely, i.m. glucagon elicited an increase in GH (baseline, 1.5±0.4 μg/l; peak, 14.2±2.7 μg/l (180 min); P < 0.01) and cortisol concentrations (baseline, 452.6±35.2 nmol/l; peak, 622.1±44 nmol/l (180 min); P < 0.01). The changes in ghrelin concentration at both 120 and 180 min were still significant after correction for glucose and insulin (P < 0.05). Conclusions: We show that i.m. glucagon decreases ghrelin significantly. Therefore, the already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations. The mechanisms underlying the ghrelin suppression after i.m. glucagon are unlikely to include glucose or insulin variations and need to be further elucidated.