Objective: To clarify the metabolic effects of an overnight intravenous infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin-receptor subtype, including effects on β-cell viability and function, insulin secretion and sensitivity, glucose and lipid metabolism. Design: We studied the effects of a 16-hours infusion (from 2100 h to 1300 h) of UAG (1.0 µg/kg/h) or saline in 8 normal subjects (age [mean±SEM]: 29.6±2.4 yrs; BMI: 22.4±1.7 kg/m(2)), who were served, at 2100 h 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 AUC values by 10% (UAG0-960min: 79.0±1.7 x103mg/dL/min vs. Saline0-960min: 87.5±3.8 x103mg/dL/min) and the AUC at night by 14% (UAG180-660min: 28.4±0.5 x103mg/dL/min vs. Saline180-660min: 33.2±1.1 x103mg/dL/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 (UAG0-960min: 0.3±0.02 x103 vs. Saline0-960min: 0.6±0.05 x103 mEq/L/min). Conclusions: The exposure to the intravenous administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of acylated ghrelin, the unacylated form of ghrelin displays hypoglycemic properties.
Metabolic effects of overnight continuous infusion of unacylated ghrelin in humans.
BENSO, Andrea Silvio;GRANATA, Riccarda;GHIGO, Ezio;BROGLIO, Fabio
2012-01-01
Abstract
Objective: To clarify the metabolic effects of an overnight intravenous infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin-receptor subtype, including effects on β-cell viability and function, insulin secretion and sensitivity, glucose and lipid metabolism. Design: We studied the effects of a 16-hours infusion (from 2100 h to 1300 h) of UAG (1.0 µg/kg/h) or saline in 8 normal subjects (age [mean±SEM]: 29.6±2.4 yrs; BMI: 22.4±1.7 kg/m(2)), who were served, at 2100 h 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 AUC values by 10% (UAG0-960min: 79.0±1.7 x103mg/dL/min vs. Saline0-960min: 87.5±3.8 x103mg/dL/min) and the AUC at night by 14% (UAG180-660min: 28.4±0.5 x103mg/dL/min vs. Saline180-660min: 33.2±1.1 x103mg/dL/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 (UAG0-960min: 0.3±0.02 x103 vs. Saline0-960min: 0.6±0.05 x103 mEq/L/min). Conclusions: The exposure to the intravenous administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of acylated ghrelin, the unacylated form of ghrelin displays hypoglycemic properties.
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