Modulatory effects of peroxovanadates on insulin receptor binding
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AbstractThe insulin-mimetic effects exhibited by vanadate, hydrogen peroxide, and some peroxovanadates have recently been shown to occur, at least in part, through an activation of the insulin receptor tyrosine kinase activity. In this study, we examine the effects of these compounds on insulin receptor binding using receptor preparations from human placental membranes. Among the 16 vanadium(V)-peroxo complexes studied, the [VO(O-2)(2)(bipy)](-) ion, where bipy = 2,2'-bipyridine, was found to increase insulin receptor binding by 24%, whereas the [VO(O-2)(2)(en)](-) ion, where en = ethylenediamine, was found to reduce insulin receptor binding by about the same amount under steady-state conditions. Scatchard analysis of the binding data indicates that the observed effect of the [VO(O-2)(2)(bipy)](-) ion on insulin receptor binding is exerted mainly at the high-capacity low-affinity sites. Furthermore, this modulatory effect is reversible and requires a continuous presence of the compound. By perturbing the membrane environment of the insulin receptor, we have shown that an intact membrane structure is essential for an observable effect. The observed modulation of insulin receptor binding by peroxovanadates is interpreted in terms of a ternary complex model in which the peroxovanadate acts as an allosteric effector modulating the binding equilibrium between insulin and its receptor.
All Author(s) ListKwong DWJ, Leung WN, Xu MH, Zhu SQ, Cheng CHK
Journal nameJournal of Inorganic Biochemistry
Year1996
Month11
Day15
Volume Number64
Issue Number3
PublisherELSEVIER SCIENCE INC
Pages163 - 180
ISSN0162-0134
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Chemistry; Chemistry, Inorganic & Nuclear; CHEMISTRY, INORGANIC & NUCLEAR

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