Metabolic effects of overnight continuous infusion of unacylated ghrelin in humans

Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin receptor subtype, including effects on beta-cell viability and function, insulin secretion and sensitivity, and glucose and lipid metabolism. Design: We studied the effects of a 16-h infusion (from 2100 to 1300 h) of UAG (1.0 mu g/kg per h) or saline in eight normal subjects (age (mean +/- S.E.M.), 29.6 +/- 2.4 years; body mass index (BMI), 22.4 +/- 1.7 kg/m(2)), who were served, at 2100 and 0800 h respectively, with isocaloric balanced dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were measured every 20 min. Results: In comparison with saline, UAG induced significant (P < 0.05) changes in glucose, insulin, and FFA profiles. UAG infusion decreased glucose area under the curve (AUC) values by 10% (UAG(0-960) (min) :79.0 +/- 1.7 X 10(3) mg/dl per min vs saline(0-960) (min): 87.5 +/- 3.8 X 10(3) mg/dl per min) and the AUC at night by 14% (UAG(180-660) (min): 28.4 +/- 0.5 X 10(3) mg/dl per min vs saline(180-660) (min): 33.2 +/- 1.1 X 10(3) mg/dl per min). The overall insulin AUC was not significantly modified by UAG infusion; however, insulin AUC observed after meals was significantly increased under the exposure to UAG with respect to saline at either dinner or breakfast. The FFA AUC values were decreased by 52% under the exposure to UAG in comparison with saline (UAG(0-960 min): 0.3 +/- 0.02 X 10(3) mEq/l per min vs saline(0-960 min): 0.6 +/- 0.05 X 10(3) mEq/l per min). Conclusions: Exposure to the i.v. administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic properties.