Uptake and metabolic effects of insulin mimetic oxovanadium compounds in human erythrocytes

Abstract

The uptake of the oxidation products of two oxovanadium(IV) compounds, [N,N'-ethylenebis(pyridoxylaminato)]oxovanadium(IV), VIVO(Rpyr2en), and bis-[3-hydroxy-1,2-dimethyl-4-pyridinonato]oxovanadium(IV), VIVO(dmpp)2, by human erythrocytes was studied using 51V and 1H NMR and EPR spectroscopy. VIVO(Rpyr2en) in aerobic aqueous solution is oxidized to its VV counterpart and the neutral form slowly enters the cells by passive diffusion. In aerobic conditions, VIVO(dmpp)2 originates VV complexes of 1:1 and 1:2 stoichiometry. The neutral 1:1 species is taken up by erythrocytes through passive diffusion in a temperature-dependent process; its depletion from the extracellular medium promotes the dissociation of the negatively charged 1:2 species, and the protonation of the negatively charged 1:1 species. The identity of these complexes is not maintained inside the cells, and the intracellular EPR spectra suggest N2O2 or NO3 intracellular coordinating environments. The oxidative stress induced by the oxovanadium compounds in erythrocytes was not significant at 1 mM concentration, but was increased by both vanadate and oxidized VIVO(dmpp)2 at 5 mM. Only 1 mM oxidized VIVO(dmpp)2 significantly stimulated erythrocytes glucose intake (0.75 ± 0.13 against 0.37 ± 0.17 mM/h found for the control, p < 0.05).