The aim of our study was to investigate whether sodium lactate has any effect on hepatic insulin dynamics in perfused rat liver. Rat livers were perfused in situ with saline or increasing concentrations of sodium lactate, and hepatic insulin extraction was calculated from the difference in insulin concentration between the portal and the suprahepatic vein. Our results show that hepatic insulin extraction at the three lactate concentrations added was higher than in the control experiments (lactate 1 mmol/l: 263 +/- 51 vs. 765 +/- 114, P < 0.005; lactate 5 mmol/l: 341 +/- 80 vs. 906 +/- 109; P < 0.005; lactate 15 mmol/l: 438 +/- 21 vs. 981 +/- 66 microIU.g-1.30 min-1, P < 0.005). No significant differences were observed in net glucose balance across the liver during perfusion with lactate. Moreover perfused liver displayed a net lactate production during infusion with saline or lactate added at the lower concentrations (1 and 5 mM), whereas at the highest (15 mM), a net lactate uptake by the liver was observed (P < 0.05). Our results suggest that, in perfused rat liver, lactate may increase hepatic insulin clearance. Thus energy fuels such as lactate and nonesterified fatty acid have opposite effects on hepatic insulin clearance and may therefore contribute to the regulation of posthepatic insulin delivery.