Differential acute effects of oxovanadiums and insulin on glucose and lactate metabolism under in vivo and in vitro conditions

Oxovanadium compounds such as vanadate and peroxovanadiums have been shown to have insulin-mimetic effects on various metabolic pathways, including glucose metabolism A differential effect of various oxovanadium species on glucose metabolism in different tissues has been reported. The results from our present in vivo studies using rats show that peroxovanadiums and insulin have similar acute effects on decreasing blood glucose levels, but: dissimilar effects on blood lactate levels. Furthermore, when bisperoxovanadate (BPV) was administered acutely to intact animals immediately before a bolus insulin challenge, it blunted the effectiveness of insulin in decreasing the blood lactate level, but at the same time demonstrated a synergistic effect on the hypoglycemic action of insulin. It was also observed in in vitro studies using normal 3T3-L1 adipocytes (not serum-deprived) that 1,10-phenanthroline bisperoxovanadate (PHEN-BPV) attenuates the incorporation of carbon from lactate but not from glucose, into lipid in both the absence and presence of insulin. Additionally, it was observed that PHEN-BPV had no effect on lactate dehydrogenase (LDH) activity Thus, one may speculate that PHEN-BPV interferes with carrier-mediated lactate transport, These observations demonstrate that insulin and oxovanadiums differ in the handling of different metabolic substrates. Thus, even though oxovanadiums mimic many of the metabolic actions of insulin, their metabolic effects are by no means identical, Moreover, since vanadate hd no acute effect on glucose metabolism under in vivo conditions, this may suggest that to be effective as a hypoglycemic agent vanadate needs to be converted to some other biologically active oxovanadium species. Finally the observed interference by PHEN-BPV in the metabolism of lactate may predispose subjects using oral vanadate, as a part of the therapeutic regimen for management of diabetic hyperglycemia, to lactic acidosis. Copyright (C) 1997 by W.B. Saunders Company.