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Originally published In Press as doi:10.1074/jbc.M110798200 on January 28, 2002

J. Biol. Chem., Vol. 277, Issue 14, 12215-12220, April 5, 2002
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Structural Origins of the Insulin-mimetic Activity of Bis(acetylacetonato)oxovanadium(IV)*

Marvin W. MakinenDagger § and Matthew J. Brady||

From the Dagger  Department of Biochemistry and Molecular Biology, Cummings Life Science Center, The University of Chicago and the  Department of Medicine, Section on Endocrinology, Albert Merritt Billings Hospital of The University of Chicago, Chicago, Illinois 60637

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-[1-14C]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 VOSO4. 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 VO2+ may be dependent on adduct formation with BSA and possibly other serum transport proteins.

* This work was supported by National Institutes of Health Grant DK20959.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, The University of Chicago, 920 East 58th St., Chicago, IL 60637. Tel.: 773-702-1080; Fax: 773-702-0439; E-mail: makinen@uchicago.edu.

|| Recipient of a Career Development Award from the American Diabetes Association.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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