Effect of domperidone on the release of insulin after intravenous glucose load in man

Abstract

To determine whether the blockade of the dopaminergic system is capable of modifying glucose-induced insulin release in man, the responses of insulin to an iv glucose load were measured at various domperidone infusion rates. The infusion of 5 μg/kg/min of domperidone increased significantly plasma insulin levels during the acute phase of glucose-induced insulin release and lowered plasma glucose values at 50 and 60 min; the k of glucose disappearance improved significantly. At lower domperidone infusion rates the acute increment of insulin after glucose load was indistinguishable from the response observed at 5 μg/kg/min until 0.5 μg/kg/min, while similar responses in control and experimental tests were observed at 0.25 μg/kg/min. A group of subjects was submitted to an arginine load in order to establish whether the effect observed with domperidone was specific for the glucose-induced insulin release; but, this time, we did not observe any significant effect during the domperidone-induced dopaminergic blockade. Furthermore, we also measured the plasma prolactin levels, to see whether the specific and well known effect of domperidone on prolactin release matches with the effect on β-cell function. As far as prolactin is concerned, we observed a dose response effect of domperidone infusion, with a detectable elevation of prolactin at infusion rate of 0.25 μg/kg/min. Since domperidone is a specific antagonist of dopamine D₂-receptors, we propose that dopamine might exert a specific inhibiting effect on glucose-induced insulin release through this class of dopamine receptors.