Evidence for selective effects of vanadium on adipose cell metabolism involving actions on cAMP-dependent protein kinase.
The insulin-like effects of vanadium in vivo are likely to be achieved at micromolar concentrations. Demonstrated effects of vanadium on adipose tissue of streptozotocin-diabetic rats include inhibition of basal and stimulated rates of lipolysis and effects on fat cell protein phosphorylation. The studies described below examined the effects of vanadium (to a maximum concentration of 0.5 mM) on adipose cells or tissue in vitro. Vanadium, added as a vanadyl-albumin complex or as sodium orthovanadate, produced a marked (greater than 50%) inhibition of isoproterenol-stimulated lipolysis. Inhibition of lipolysis equivalent to that seen with insulin, was achieved with approximately 100 microM vanadium. In contrast, no insulin-like stimulation of de novo fatty acid biosynthesis was observed with vanadium below 0.5 mM. Surprisingly, the antilipolytic effects of vanadium persisted in the presence of cilostamide, an inhibitor of the insulin-sensitive isoform of cyclic nucleotide phosphodiesterase. Studies with purified preparations of the catalytic subunit of cyclic AMP-dependent protein kinase revealed dose-dependent inhibition with vanadyl-glutathione (to a maximum of approximately 40% inhibition). Equivalent inhibition of cyclic AMP-dependent phosphorylation of Kemptide (approximately 50%) was observed upon incubation of freshly-prepared fat-pad supernatant fractions with vanadyl-glutathione. These results suggest that effects of low concentrations of vanadium may be mediated, at least in part, by actions on the catalytic subunit of cyclic AMP-dependent protein kinase.
Brownsey
R W
RW
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
Dong
G W
GW
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017968:Vanadium Compounds / Q000494:pharmacology*
D017968:Vanadium Compounds; D017868:Cyclic AMP-Dependent Protein Kinases