Evidence for the Distinct Vanadyl(+4)-Dependent Activating System for Manifesting Insulin-Like Effects

Both exogenously added vanadate (oxidation state +5) and vanadyl (oxidation state +4) mimic the rapid responses of insulin through alternative signaling pathways, not involving insulin receptor activation [reviewed in Shechter et al. (1995) Mol. Cell. Biochem. 153, 39−47]. Vanadium exhibits complex...

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Bibliographic Details
Published in:Biochemistry (Easton) 1996-06, Vol.35 (25), p.8314-8318
Main Authors: Li, Jinping, Elberg, Gerard, Crans, Debbie C, Shechter, Yoram
Format: Article
Language:English
Subjects:
Adipocytes - drug effects
Animals
Cytosol - enzymology
Dose-Response Relationship, Drug
Enzyme Activation
Glutathione - pharmacology
Hypoglycemic Agents - pharmacology
Insulin - pharmacology
Lipids - biosynthesis
Male
Molecular Mimicry
Oxidation-Reduction
Protein-Tyrosine Kinases - metabolism
Rats
Rats, Wistar
Signal Transduction
Vanadium Compounds - pharmacology
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Summary:Both exogenously added vanadate (oxidation state +5) and vanadyl (oxidation state +4) mimic the rapid responses of insulin through alternative signaling pathways, not involving insulin receptor activation [reviewed in Shechter et al. (1995) Mol. Cell. Biochem. 153, 39−47]. Vanadium exhibits complex chemistry, fluctuating between vanadate(+5) and vanadyl(+4), according to the prevailing conditions. Using several experimental approaches, we report here on a distinct vanadate(+5)-independent, vanadyl(+4)-dependent activating pathway. The key components of this pathway are membrane protein phosphotyrosine phosphatases (PTPases) and a cytosolic (nonreceptor) protein-tyrosine kinase (CytPTK). We further suggest that vanadate(+5) is not reduced rapidly to vanadyl(+4) inside the cell, and entered vanadyl sulfate(+4) is capable of undergoing spontaneous oxidation to vanadate(+5) in vivo. Finally, we show that the promotion and full expression of a downstream bioeffect such as lipogenesis requires both activation of CytPTK and prolonged stability of vanadyl(+4) against oxidation.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi960209i