Organic Vanadium Chelators Potentiate Vanadium-Evoked Glucose Metabolism In Vitro and In Vivo: Establishing Criteria for Optimal Chelators

Several ligands, when complexed with vanadium, potentiate its insulinomimetic activity both in vivo and in vitro. We have recently found that l-Glu-γ-monohydroxamate (HXM) andl-Asp(β)HXM were especially potent in this regard. In the present study, we used vanadium-enriched adipose cells and cell-free experimental systems to determine the features ofl-Glu(γ)HXM and l-Asp(β)HXM that turn these ligands into optimal-synergizing vanadium chelators. We found thatl-Glu(γ)HXM and l-Asp(β)(HXM) possess the following characteristics: 1) They associate with vanadium(+5) at pH 7.2 within a narrow range of an apparent formation constant of 1.3 to 1.9 × 102 M−1; 2) they have nearly the same binding affinity for the vanadyl(+4) cation and the vanadate(+5) anion at physiological pH values; and 3) they form intense ultraviolet absorbing complexes upon associating with vanadium(+4) at 1 and 3 M stoichiometry, respectively, at pH 3.0. Vanadium ligands lacking any of these three defined criteria synergize less effectively with vanadium to activate glucose metabolism.