The present study was designed to determine the effect of low dose continuous and oscillatory intraportal insulin infusions upon subsequent glucose-induced insulin release. In overnight-fasted and anesthetized rats with indwelling catheters in the jugular vein, carotid artery, and mesenteric vein insulin was infused intraportally for 3 h via the mesenteric vein catheter at a continuous rate of 45 microU/kg X min, or the same amount of insulin was administered at alternating high (72 microU/kg X min) and low infusion rates (18 microU/kg X min), respectively, in 2-, 4-, 8-, and 16-min cycles (oscillatory infusions). Another group received a continuous infusion of saline. Glucose (0.4 g/kg) was given i.v. 30 min after the end of the insulin or saline infusion. During the 3-h infusion of insulin or saline the peripheral glucose level remained unchanged in all groups. In response to the i.v. glucose load peripheral arterial plasma insulin levels were significantly elevated after preceding oscillatory infusions compared to the continuous insulin infusion. As compared to the group receiving saline the glucose-induced insulin response after continuous insulin infusion was significantly reduced. The plasma glucose responses were not different except for inexplicably elevated glucose levels in the 4-min cycle group. No difference was observed for plasma glucagon levels in all groups. The present data demonstrate an augmented responsiveness of the beta-cell to glucose after a preceding oscillatory infusion of insulin and an impaired responsiveness to glucose after continuous insulin infusion. This indicates that an oscillatory insulin release might be of importance for an adequate regulation of beta-cell function.