COMPARISON OF THE GLUCOSE-LOWERING PROPERTIES OF VANADYL SULFATE AND BIS(MALTOLATO)OXOVANADIUM(IV) FOLLOWING ACUTE AND CHRONIC ADMINISTRATION

Numerous studies, bath in vitro and in vivo, have demonstrated the ins ulin-mimetic properties of vanadium. Chronic oral administration of in organic and organic compounds of both vanadium(IV) and vanadium(V) red uced plasma glucose levels and restored plasma lipid levels in strepto zotocin-diabetic rats. We investigated the acute effects of both vanad yl sulfate and bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadi um compound, on plasma glucose levels by several routes of administrat ion. Previous studies have shown that chronic administration of vanady l sulfate has resulted in a sustained euglycemia following withdrawal of the drug. This effect was not observed following the chronic admini stration 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 bo th vanadyl sulfate and BMOV when administered as a single dose by eith er oral gavage or intraperitoneal injection. In those animals that res ponded to vanadium treatment, plasma glucose levels were within the no rmal 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 tr eatment 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 o n 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 wa s 2 to 3 times as potent as vanadyl sulfate. This difference in potenc y was observed with both oral and intraperitoneal administration, whic h suggests that the increase in potency with BMOV cannot be totally at tributed to increased gastrointestinal absorption. Organic chelation o f vanadium may facilitate uptake into vanadium-sensitive tissues. Chro nic oral administration of higher concentrations of BMOV did not resul t in a sustained reduction in plasma glucose following withdrawal of t he drug. All diabetic rats eventually responded to increased concentra tions of BMOV with a restoration of plasma glucose levels to normal va lues; however, reversion to the hyperglycemic state occurred within 2 days of withdrawal of treatment. Chronic oral administration of BMOV d id not produce a sustained euglycemic effect following withdrawal, but acute administrations of the compound by either oral gavage or intrap eritoneal injection did produce a long-term reduction in plasma glucos e levels. Rats treated chronically with vanadyl sulfate remained eugly cemic even after the drug was withdrawn. However, acute treatment prod uced only a transient euglycemia.