Numerous studies, both in vitro and in vivo, have demonstrated the
insulin-mimetic properties of
vanadium. Chronic
oral administration of inorganic and organic compounds of both
vanadium(IV) and
vanadium(V) reduced plasma
glucose levels and restored plasma
lipid levels in
streptozotocin-diabetic rats. We investigated the acute effects of both
vanadyl sulfate and
bis(maltolato)oxovanadium(IV) (BMOV), an organic
vanadium compound, on plasma
glucose levels by several routes of administration. Previous studies have shown that chronic administration of
vanadyl sulfate has resulted in a sustained euglycemia following withdrawal of the
drug. This effect was not observed following the chronic administration of BMOV; therefore, we investigated the effect of increasing the concentration of BMOV on the production of a sustained euglycemic response. An acute plasma
glucose lowering effect was obtained with both
vanadyl sulfate and BMOV when administered as a single dose by either oral gavage or
intraperitoneal injection. In those animals that responded to
vanadium treatment, plasma
glucose levels were within the normal range within 2 to 6 h when given by i.p. injection or within 4 to 8 h when given by oral gavage. BMOV-treated rats that responded to treatment maintained the euglycemic effect for extended periods, ranging from 1 to 14 weeks following administration. However,
vanadyl sulfate treated rats reverted to
hyperglycemia within 12 to 24 h, depending on the route of administration.
Intravenous administration of BMOV was effective in lowering plasma
glucose levels only when administered by continuous infusion. An oral dose-response curve showed that BMOV was 2 to 3 times as potent as
vanadyl sulfate. This difference in potency was observed with both oral and intraperitoneal administration, which suggests that the increase in potency with BMOV cannot be totally attributed to increased gastrointestinal absorption. Organic chelation of
vanadium may facilitate uptake into
vanadium-sensitive tissues. Chronic
oral administration of higher concentrations of BMOV did not result in a sustained reduction in plasma
glucose following withdrawal of the
drug. All diabetic rats eventually responded to increased concentrations of BMOV with a restoration of plasma
glucose levels to normal values; however, reversion to the hyperglycemic state occurred within 2 days of withdrawal of treatment. Chronic
oral administration of BMOV did not produce a sustained euglycemic effect following withdrawal, but acute administration of the compound by either oral gavage or
intraperitoneal injection did produce a long-term reduction in plasma
glucose levels. Rats treated chronically with
vanadyl sulfate remained euglycemic even after the
drug was withdrawn. However, acute treatment produced only a transient euglycemia.