IN-VIVO AND IN-VITRO STUDIES OF VANADATE IN HUMAN AND RODENT DIABETES-MELLITUS

In vivo vanadate and vanadyl have been shown to mimic the action of in sulin and to be effective treatment for animal models of both Type I a nd Type II diabetes. The molecular mechanism of action of the vanadium salts on insulin sensitivity remains uncertain, and several potential sites proposed for the insulin-like effects are reviewed. In human tr ials, insulin sensitivity improved in patients with NIDDM, as well as in some patients with IDDM after two weeks of treatment with sodium me tavanadate. This increase in insulin sensitivity was primarily due to an increase in non-oxidative glucose disposal, whereas oxidative gluco se disposal and both basal and insulin stimulated suppression of hepat ic glucose output (HGP) were unchanged. Clinically, oral vanadate was associated with a small decrease in insulin requirements in IDDM subje cts. Of additional benefit, there was a decrease in total cholesterol levels in both IDDM and NIDDM subjects. Furthermore, there was an incr ease in the basal activities of MAP and S6 kinases to levels similar t o the insulin-stimulated levels in controls, but there was little or n o further stimulation with insulin was seen. Further understanding of the mechanism of vanadium action may ultimately be useful in the desig n of drugs that improve glucose tolerance.