VANADATE HAS NO EFFECT ON INSULIN-EXTRACTION BY THE RAT-LIVER

The mechanism(s) responsible for the insulin-like effects of vanadate are still unclear, although several possible explanations have been ra ised. However, the possibility that vanadate induces inhibition of ins ulin degradation in the liver was not examined yet. Therefore, in the present study we examined the effect of vanadate on the extraction of insulin by the perfused rat liver using an open, non-recycling system. Baseline insulin extraction (44+/-2% and 37+/-3%) was not affected by the administration of 1 and 5 mu M vanadate (decreased to 42+/-2% and 36+/-1%, respectively, p = NS). Vanadate had no adverse effects on li ver viability, and the bile flow remained stable during and after vana date administration (0.87+/-0.08 mu l/min/g liver prior to Vs. 0.084+/ -0.11 mu l/min/g liver following vanadate administration). This study shows that vanadate does not inhibit insulin extraction by the perfuse d liver, and that doses of vanadate that effectively inhibit hepatic g lucose production possess no adverse effects on liver viability.