MedWire News: Results from a proof-of-concept study show that ghrelin reduces glucose-stimulated insulin secretion and subsequently lowers plasma glucose in healthy nondiabetic individuals.
"Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve β-cell function," say Jenny Tong (University of Cincinnati, Ohio, USA) and colleagues.
For their study, the researchers recruited 12 healthy, nondiabetic volunteers (eight men, four women) aged 18-55 years and with a body mass index (BMI) between 18 and 29 kg/m2.
The participants were given an infusion of saline, or ghrelin 0.3, 0.9, or 1.5 nmol/kg/hour for more than 65 minutes on four separate occasions separated by at least 5 days. The team then measured fasting insulin and glucose, and intravenous glucose tolerance (glucose disappearance constant; Kg) and the acute insulin response to intravenous glucose (AIRg).
Tong and co-workers found that, compared with saline, the three ghrelin infusions did not significantly change fasting plasma insulin or glucose levels.
However, AIRg was significantly decreased by the three concentrations of ghrelin to 1478, 1419, and 1120 pmol/l after the ghrelin 0.3, 0.9, and 1.5 nmol/kg/hour infusions, respectively, compared with 2152 pmol/l with saline.
C-peptide concentration was also suppressed in the three ghrelin groups versus saline, at a respective 4.1, 4.2, and 3.6 nmol/l versus 5.8 nmol/l. Kg was significantly reduced after ghrelin 0.3 and 1.5 nmol/kg/hour infusions to 1.00 and 1.05 %change/min, respectively, compared with 1.40 %change/min with saline.
"Preclinical studies support a role for ghrelin to regulate glucose metabolism as well as energy balance and growth hormone secretion," write the authors in the journal Diabetes.
"However, the effect of ghrelin on insulin secretion and glucose tolerance in humans has not been clearly established in the limited number of studies reported previously."
Tong et al conclude: "Our study demonstrates that exogenous ghrelin markedly reduces the first-phase insulin and C-peptide responses to intravenous glucose in healthy humans."
They add that ghrelin antagonists have the potential to improve β-cell function and say they could provide a novel drug target for the treatment of Type 2 diabetes.
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