NON-INSULIN-LIKE ACTION OF SODIUM ORTHOVANADATE IN THE ISOLATED-PERFUSED LIVER OF FED, NONDIABETIC RATS

Vanadium compounds exert insulin-like effects on isolated rat adipocytes and skeletal muscle and improve glucose homeostasis in diabetic rats and mice. However, reports on metabolic actions of vanadium in the liver are still contradictory. Thus, the acute effect of sodium orthovanadate infusion on net glucose production was measured in isolated perfused livers of non-fasting, non-diabetic rats. Continuous infusion (0.2 ml/min; 90 min) of vanadate (10-500 mumol/1) rapidly increased hepatic glucose (p < 0.001), but not cyclic AMP output, reaching peak values after 20 min. The cumulative glucose release displayed concentration dependence with a maximal net effect of 394.3 mumol/100 g body weight and an apparent half-maximal effective vanadate concentration of 19.6 mumol/l. The glycogenolytic response to vanadate was almost completely blocked by 100 mU/l insulin (p < 0.005), by 0.1 mmol/l indomethacin (p < 0.05) and in the absence of Ca2+ (p < 0.001). These results indicate that sodium orthovanadate stimulates glycogenolysis in livers of fed, non-diabetic rats by a Ca2+-dependent mechanism, which may involve the release of prostaglandins.