Our aim was to clarify the effect of a somatostatin analogue (octreotide) on glucose flux in conscious dogs. We monitored the effects with catheters in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery before and after oral glucose administration. A significant increase of portal vein plasma flow after oral glucose was completely suppressed by both 4 and 1 micrograms/kg octreotide. All doses of octreotide (4, 1 and 0.1 microgram/kg) suppressed the glucose-induced increment of arterial glucose by dose response. Only 4 micrograms/kg of octreotide slightly but significantly suppressed hepatic glucose output. Marked suppression and delayed glucose absorption by the intestine was observed after 4 micrograms/kg of octreotide. One and 0.1 microgram/kg octreotide also suppressed glucose absorption without delayed absorption. Total amounts of absorbed glucose during 3h after oral glucose were 24 +/- 11% with 4 micrograms/kg of octreotide, 37 +/- 16% with 1 microgram/kg of octreotide, and 48 +/- 8% with 0.1 microgram/ kg of octreotide, all of which were significantly less than that of the control (73 +/- 8%). Using 4 micrograms/kg of octreotide treatment, the liver took up only 5 +/- 4% of the absorbed glucose, while the liver took up 35 +/- 6% and 43 +/- 9% of the absorbed glucose with 1 and 0.1 microgram/kg of octreotide. These latter values were similar to that of the control value of 34 +/- 4%. In conclusion, we found that octreotide administered before oral glucose had a remarkable stabilizing effect on postprandial glycemic surges. Both the direct inhibitory effect of octreotide on portal vein plasma flow and impaired glucose absorption would contribute to this decreased postprandial hyperglycemia, while its suppressive effect on other hormones, such as insulin and glucagon, did not seem to influence the reduction of hyperglycemia.