Glucose-dependent insulinotropic polypeptide (GIP), is an incretin with important role in glucose homeostasis and energy conservation. Thus far, the neural/hormonal mechanisms involved in the regulation of GIP secretion, have not yet been fully elucidated. The aim of this study was to evaluate a possible effect of intracerebroventricular administration of insulin in a centrally mediated regulation of GIP.Twenty-four adult dogs were used in this study. In group 1 the animals received a bolus icv infusion of regular insulin in a total volume of 50 microl or an equivalent amount of artificial cerebrospinal fluid (aCSF). In group 2 the animals received a continuous icv infusion of insulin or aCSF over a 3-h period. In group 3 the experiment of group 2 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann-Bollman fistula. Blood samples were taken from cannulation of a hind limb vein at -15, 0, 5, 10, 15, 30, 45, 60, 90, 120, 150 and 180 min after infusions. Plasma levels of glucose, insulin and GIP were assayed.Insulin levels were increased significantly in group 2 and 3 while GIP secretion was partly inhibited after icv administration of insulin and intraduodenal administration of glucose in the 3rd group.It is suggested that the hypothalamic insulin signaling contributes to plasma insulin levels and possibly exerts a negative regulation of GIP secretion after glucose load.