Structural origins of the insulin-mimetic activity of bis(acetylacetonato)oxovanadium(IV).
We have investigated the interaction of bis(acetylacetonato)oxovanadium(IV) (VO(acac)(2)) with bovine serum albumin (BSA) by EPR and angle-selected electron nuclear double resonance, correlating results with assays of glucose uptake by 3T3-L1 adipocytes. EPR spectra of VO(acac)(2) showed no broadening in the presence of BSA; however, electron nuclear double resonance titrations of VO(acac)(2) in the presence of BSA were indicative of adduct formation of VO(acac)(2) with albumin of 1:1 stoichiometry. The influence of VO(acac)(2) on uptake of 2-deoxy-d-[1-(14)C]glucose by serum-starved 3T3-L1 adipocytes was measured in the presence and absence of BSA. Glucose uptake was stimulated 9-fold in the presence of 0.5 mm VO(acac)(2), 17-fold in the presence of 0.5 mm VO(acac)(2) plus 1 mm BSA, and 22-fold in the presence of 100 nm insulin. BSA had no influence on glucose uptake, on the action of insulin, or on glucose uptake in the presence of VOSO(4). The maximum insulin-mimetic effect of VO(acac)(2) was observed at VO(acac)(2):BSA ratios less than or equal to 1.0. Similar results were obtained also with bis(maltolato)oxovanadium(IV). These results suggest that the enhanced insulin-mimetic action of organic chelates of VO(2+) may be dependent on adduct formation with BSA and possibly other serum transport proteins.
Makinen
Marvin W
MW
Department of Biochemistry and Molecular Biology, Cummings Life Science Center, The University of Chicago, Illinois 60637, USA. makinen@uchicago.edu
Brady
Matthew J
MJ
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D004583:Electrons; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism
D007328:Insulin; D009942:Organometallic Compounds; D012709:Serum Albumin; C054082:oxobis(acetylacetonato)vanadium IV