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Evidence for selective effects of vanadium on adipose cell metabolism involving actions on cAMP-dependent protein
1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
Abstract:
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.
Insights
Vanadium exhibits insulin-like effects by inhibiting lipolysis in adipose cells at micromolar concentrations. These effects may involve actions on cyclic AMP-dependent protein kinase, impacting fat metabolism.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- Vanadium compounds demonstrate insulin-like effects in vivo, particularly on adipose tissue in diabetic rats.
- Observed effects include modulation of lipolysis and protein phosphorylation in fat cells.
Purpose of the Study:
- To investigate the in vitro effects of vanadium on adipose cells and tissue.
- To elucidate the specific mechanisms underlying vanadium's insulin-like actions, focusing on lipolysis and protein phosphorylation.
Main Methods:
- Vanadium (vanadyl-albumin complex or sodium orthovanadate) was added to adipose cells/tissue in vitro (up to 0.5 mM).
- Lipolysis was stimulated using isoproterenol; fatty acid biosynthesis was measured.
- Effects on cyclic AMP-dependent protein kinase and its substrates were assessed using purified enzymes and fat-pad supernatant fractions.
Main Results:
- Vanadium significantly inhibited isoproterenol-stimulated lipolysis, comparable to insulin, at approximately 100 microM.
- No insulin-like stimulation of de novo fatty acid biosynthesis was observed below 0.5 mM vanadium.
- Vanadium's antilipolytic effects persisted despite the presence of cilostamide.
- Vanadyl-glutathione dose-dependently inhibited cyclic AMP-dependent protein kinase activity and Kemptide phosphorylation.
Conclusions:
- Low concentrations of vanadium exert insulin-like antilipolytic effects in adipose tissue.
- These effects appear to be mediated, in part, by direct actions on the catalytic subunit of cyclic AMP-dependent protein kinase.
- Vanadium's mechanism differs from insulin regarding fatty acid biosynthesis and is not solely dependent on phosphodiesterase inhibition.