Uptake and metabolic effects of insulin mimetic oxovanadium compounds in human erythrocytes.
The uptake of the oxidation products of two oxovanadium(IV) compounds, [N,N'-ethylenebis(pyridoxylaminato)]oxovanadium(IV), V(IV)O(Rpyr(2)en), and bis-[3-hydroxy-1,2-dimethyl-4-pyridinonato]oxovanadium(IV), V(IV)O(dmpp)(2), by human erythrocytes was studied using (51)V and (1)H NMR and EPR spectroscopy. V(IV)O(Rpyr(2)en) in aerobic aqueous solution is oxidized to its V(V) counterpart and the neutral form slowly enters the cells by passive diffusion. In aerobic conditions, V(IV)O(dmpp)(2) originates V(V) 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 N(2)O(2) or NO(3) intracellular coordinating environments. The oxidative stress induced by the oxovanadium compounds in erythrocytes was not significant at 1mM concentration, but was increased by both vanadate and oxidized V(IV)O(dmpp)(2) at 5mM. Only 1mM oxidized V(IV)O(dmpp)(2) significantly stimulated erythrocytes glucose intake (0.75+/-0.13 against 0.37+/-0.17mM/h found for the control, p<0.05).
Delgado
Teresa C
TC
Department of Biochemistry, Center of NMR Spectroscopy and Center for Neurosciences and Cell Biology, University of Coimbra, P.O. Box 3126, 3001-401 Coimbra, Portugal.
Tomaz
A Isabel
AI
Correia
Isabel
I
Costa Pessoa
João
J
Jones
John G
JG
Geraldes
Carlos F G C
CF
Castro
M Margarida C A
MM
D000328:Adult; D001693:Biological Transport, Active; D001786:Blood Glucose / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014638:Vanadates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D008024:Ligands; C075743:oxovanadium IV; D014638:Vanadates