(4-Hydroxypyridine-2,6-dicarboxylato)oxovanadate(V) - A new insulin-like compound: Chemistry, effects on myoblast and yeast cell growth and effects on hyperglycemia in rats with STZ-induced diabetes

A new insulin mimetic vanadium(V) complex is introduced: (4-hydroxypyridine-2,6-dicarboxylato)oxovanadate(V). The compound was designed based on the desire to make a compound with more favorable chemical and insulin-enhancing properties than the parent (pyridine-2,6-dicarboxylato)oxovanadate(V). The solution chemistry was characterized and the complex was found to be more stable at neutral pH and to have a different lability pattern than the parent complex. The effect of the compound and its parent was investigated in various biological systems including cell culture, yeast and streptozotocin (STZ)-induced diabetic rats. The growth of myoblast cells (L6) was inhibited by both the parent and the modified vanadium(V) complex. Since the complexes have limited stability at neutral pH, yeast growth (pH range from 3.0 to 7.0) was employed as an adjunct cell model. The effect of the parent compound on inhibition of yeast cell growth was found to be pH dependent. These studies support the hypothesis that the modified complex would be more active as an insulin-enhancing agent because of its greater stability at neutral pH. The effect of (4-hydroxypyridine-2,6-dicarboxylato)oxovanadate(V) on hyperglycemia in rats with STZ-induced diabetes was determined. This complex was found to lower the diabetic hyperglycemia and joined the ranks of the few vanadium(V) complexes that have been shown to have insulin-enhancing properties in a diabetic animal model system.