In Vitro and In Vivo Effect of Acylated and Unacylated Ghrelin on Neonatal Glucose Homeostasis

Abstract

Maintenance of normal glucose homeostasis is crucial for survival during the perinatal period. Acylated ghrelin (AG) but not unacylated ghrelin (UAG) inhibits insulin release from pancreatic islets in adult rats. Circulating AG concentrations are low in the fetus and progressively increase in the postnatal period. We tested the hypothesis that AG has insulinostatic effects in vitro and in vivo during the perinatal period. In vitro, AG (10(-10)-10(-8) M) caused a 25-53% decrease in insulin secretion by islets from 5-d-old rat pups under normo- and hyperglycemic conditions, an effect that was mediated through the growth hormone secretagogue receptor (GHSR- 1a). Ghrelin (1-5) amide, [Dap3]-octanoyl, a pentapeptide that is resistant to deacylation and binds the GHSR-1a, had similar effects at 10(-8) M. In vivo, AG, UAG, or GHRP-6 [D-Lys3], a GHSR-1a antagonist, did not affect insulin or glucagon concentrations during the first 3 h of life. In 6-d-old pups, AG, UAG, or ghrelin (1-5) amide, [Dap3]-octanoyl did not affect glucose-induced insulin or C-peptide concentrations. In summary, AG has insulinostatic effects in vitro as early as during the perinatal period. These effects could not be confirmed in vivo, possibly due to the short half-life of AG in rat neonates.