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 had 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.