UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.