Insulin-enhancing vanadium compounds structure

EPR methods have uncovered a number of properties of insulin-enhancing vanadium compounds that would otherwise be difficult, if not impossible, to obtain by other methods. The strengths of EPR spectroscopy, such as its natural selectivity, the high-resolving power of closely related structural isomers, and ease of in-vivo application have been exploited to reveal important details regarding the solution chemistry, absorption, metabolism, and bioaccumulation of antidiabetic vana-... 

Recent developments in the in-vivo characterization of putative vanadium(IV) pharmaceuticals have focused on completion of a metabolic model that fully describes the Absorption, Distribution, Metabolism, and Elimination (ADME) of exogenous vanadium [23]. Such knowledge would assist in the development of compounds with increased efficacy, as direct in-vivo/in-vitro antidiabetic assays combined with complete ADME data for the putative complex would lead to an understanding of the structure/function relationships that determine a complex s insulin-enhancing capability. 

The inhibition of PTPs by vanadate is of particular interest since this mode of action is supposed to be the primary effect exerted by vanadium applied as an insulin-mimetic agent (see 5.1.1.5). The vanadate-inhibited PTP-IB VIII in Figure 5.19, the structure of which was revealed both by single-crystal X-ray diffraction and two-dimensional H- N NMR spectroscopy, was prepared by treating the phosphatase with either vanadyl sulfate or bis(maltolato)oxovanadium(lV) (BMOV) (7a in Figure 5.2). Irrespective of the nature of the intrinsically applied vanadium species, the same compound with incorporated vanadate(V) was obtained, nicely demonstrating that the active species is vanadate(V), formed by elimination of the ligands and oxidation of to V. In vivo studies further showed that intracellular PTP-IB from rat heart tissue was actively inhibited, and autophosphorylation of the insulin receptor concomitantly enhanced. 

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