By Alan Shaver, Jesse B. Ng, David A. Hall, Barry I. Posner (auth.), Ashok K. Srivastava, Jean-Louis Chiasson (eds.)

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Further studies indicated that chronic administration of vanadate markedly increased the insulin-mediated glucose uptake in the muscle, without altering the number of glucose transporters [21]. Altogether, these studies indicated that vanadate (but not insulin) is able to increase glucose metabolism in these rodents and, therefore, to induce normoglycemia in the whole animal model. Moreover, vanadium therapy markedly increased tissue responsiveness to insulin. Sites of insulin and vanadate action The insulin receptor (InsRTK) is a large transmembrane glycoprotein composed of two 135 kDa a subunits and two 95 kDa ~ subunits linked by disulfide bonds to form a ~-a­ a-~ heterotetramer [22-24].

Peroxovanadium compounds: Biological actions and mechanism of insulin-mimesis A. Paul Bevan, Paul G. , Alan Shaver2 and Barry I. Posner Polypeptide Hormone Laboratory, IMcGill Nutrition and Food Science Centre, and zDepartment of Chemistry, McGill University, Montreal, Quebec, H3A 2B2, Canada Abstract When used alone, both vanadate and hydrogen peroxide (HP) are weakly insulin-mimetic, while in combination they are strongly synergistic due to the formation of aqueous peroxovanadium species p V(aq)" Administration of these p V(aq) species leads to activation of the insulin receptor tyrosine kinase (IRK), autophosphorylation at tyrosine residues and inhibition of phosphotyrosine phosphatases (PTPs).

Recently, radical intermediates have been observed in the decomposition of peroxovanadium species in protic and aprotic media [23]. Biochemical interactions of peroxo heteroligand vanadates in the biomatter are very complex essentially because of the following three characteristic properties ofV(V) and V(IV) ions: 1) the redox interplay ofV(V)N(IV), which can overlap with peroxide and Fe(III)/Fe(II) redox processes, including the generation of radicals; 2) the stereochemical nonrigidity of V(V) andV(lV), enabling low energy rearrangements of the coordination numbers 4, 5, 6 and 7; and 3) the lability of ligands at coordination sites, which enables a rapid exchange of donor atoms in vanadium coordination sphere [12].

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