Showing papers on "Vanadate published in 2001"
TL;DR: In this article, the authors studied the energy transfer process in vanadate-doped nanocrystalline YVO4 and YP0.95V0.05O4 and showed that vanadates can be quenched at surface sites.
Abstract: The luminescence of pure and europium-doped nanocrystalline YVO4 and YP0.95V0.05O4 and the energy transfer processes in such nanoparticles have been studied by temperature dependent luminescence spectroscopy and luminescence lifetime measurements. The results indicate thermally activated energy transfer between adjacent vanadate groups in YVO4 at temperatures above 100 K, but energy transfer to europium seems to take place from direct vanadate neighbors only. In contrast to the luminescence decay of europium, the kinetic of the vanadate luminescence strongly depends on the choice of surface capping and solvent, indicating partial quenching of the vanadate emission at surface sites. The strong competition with energy transfer to surface sites seems to be reason for the absence of energy transfer to europium from distant vanadate groups. The latter explains the low room-temperature quantum yield of 15% of YVO4:Eu colloids.
185 citations
TL;DR: The crystal structure of the SurE protein from Thermotoga maritima is determined and the structural and functional analyses identify the proteins as a novel family of metal ion-dependent phosphatases.
Abstract: Homologs of the Escherichia coli surE gene are present in many eubacteria and archaea. Despite the evolutionary conservation, little information is available on the structure and function of their gene products. We have determined the crystal structure of the SurE protein from Thermotoga maritima. The structure reveals the dimeric arrangement of the subunits and an active site around a bound metal ion. We also demonstrate that the SurE protein exhibits a divalent metal ion-dependent phosphatase activity that is inhibited by vanadate or tungstate. In the vanadate- and tungstate-complexed structures, the inhibitors bind adjacent to the divalent metal ion. Our structural and functional analyses identify the SurE proteins as a novel family of metal ion-dependent phosphatases.
185 citations
TL;DR: The results suggest that dissociation of the V-ATPase complex in vivo is controlled both by the cellular environment and by the 100-kDa a-subunit isoform present in the complex.
160 citations
TL;DR: H2O2 is the species responsible for vanadate-induced G2/M phase arrest, and several regulatory pathways are involved: activation of p21, an increase of Chk1 expression and inhibition of Cdc25C, which results in phosphorylation of CDC2 and possible inactivation of cyclin B1/Cdc2 complex.
122 citations
TL;DR: The ability of living promastigotes of Leishmania amazonensis to hydrolyze extracellular ATP and a comparison between the Mg(2+)-dependent ATPase activity of virulent and avirulent promastIGotes showed that avirulence promastsigotes were less efficient than the virulent promASTigotes in hydrolyzing ATP.
114 citations
TL;DR: It is suggested that substrates modulate the rate of ATPase activity of Pgp by controlling the rateof dissociation of ADP following ATP hydrolysis and that ADP release is the rate-limiting step in the normal catalytic cycle of PGP.
99 citations
TL;DR: In this paper, vanadate (sodium orthovanadate), an inhibitor of phosphotyrosine phosphatases (PTPs), mimics many metabolic actions of insulin in vitro and in vivo.
95 citations
TL;DR: It is demonstrated that H2O2 plays an important role in vanadium-induced NFAT transactivation in two different cell types, suggesting that H 2O2 may be involved in activation of calcium-calcineurin pathways for NFAT activation caused by vanadium exposure.
78 citations
TL;DR: Results substantiated that acute and chronic administration of benzylamine with low dosages of vanadate have potent antidiabetic effects in rats.
Abstract: Semicarbazide-sensitive amine oxidase (SSAO) is highly expressed in adipose cells, and substrates of SSAO, such as benzylamine, in combination with low concentrations of vanadate strongly stimulate glucose transport and GLUT4 recruitment in 3T3-L1 and rat adipocytes. Here we examined whether acute and chronic administration of benzylamine and vanadate in vivo enhances glucose tolerance and reduces hyperglycemia in diabetic rats. Acute intravenous administration of these drugs enhanced glucose tolerance in nondiabetic rats and in streptozotocin (STZ)-induced diabetic rats. This occurred in the absence of changes in plasma insulin concentrations. However, the administration of benzylamine or vanadate alone did not improve glucose tolerance. The improvement caused by benzylamine plus vanadate was abolished when rats were pretreated with the SSAO-inhibitor semicarbazide. Chronic administration of benzylamine and vanadate exerted potent antidiabetic effects in STZ-induced diabetic rats. Although daily administration of vanadate alone (50 and 25 μmol · kg−1 · day−1 i.p.) for 2 weeks had little or no effect on glycemia, vanadate plus benzylamine reduced hyperglycemia in diabetic rats, enhanced basal and insulin-stimulated glucose transport, and upregulated GLUT4 expression in isolated adipocytes. In all, our results substantiated that acute and chronic administration of benzylamine with low dosages of vanadate have potent antidiabetic effects in rats.
71 citations
TL;DR: Oral administration in vivo experiments on the blood glucose level of streptozotocin-induced diabetes mice and the insulin-mimetic effects of metal-oxide clusters of all-inorganic composition suggest that not only monomeric tungstate and vanadate, but also the structure factors of tung state andVanadate clusters, can play a significant role in their biological action.
70 citations
TL;DR: The results show that α2 differs from α1 primarily by a shift in the E 1 ⇌E 2 equilibrium in favor of E 1 form(s) as evidenced by a ∼20-fold increase in IC50 for vanadate, and notable stability of Na,K-ATPase activity at acidic pH.
TL;DR: The speed, reversibility and dose-response of PMCA inhibition by vanadate in intact human red cells is reported, with results similar to that described for the Ca2+-ATPase in isolated red cell membranes.
TL;DR: In this article, the processing conditions, microstructure, and dielectric properties of strontium bismuth niobate vanadate ceramics, with 0 ≤x≤ 0.3, were systematically studied.
Abstract: The processing conditions, microstructure, and dielectric properties of strontium bismuth niobate vanadate ceramics, SrBi2(VxNb1−x)2O9 (SBVN, with 0 ≤x≤ 0.3), were systematically studied. A relative density of >90% was obtained for all the samples using a two-step sintering process. XRD showed that a single phase with the layered perovskite structure of SrBi2Nb2O9 (SBN) was formed with a vanadium content of up to 30 at.%. SEM revealed that the average grain size decreased gradually with an increase in vanadium content. The Curie point was found to gradually increase from ∼418°C for SBN to ∼459°C for SBVN with 30 at.% vanadium. Dielectric constants at room temperature and their respective Curie points were found to peak at a composition with 10–15 at.%; vanadium. Moreover, a high concentration of vanadium (>5 at.%) resulted in a significant increase in tangent loss at low frequencies (<1000 Hz). The relationships between chemical composition, processing condition, microstructure, and dielectric properties of SBVN ferroelectric ceramics are discussed.
TL;DR: It is suggested that IFN-α stimulation of Stat-dependent genes is necessary, but not sufficient, for this cytokine to induce apoptosis, and another signaling cascade that involves the activity of a protein-tyrosine phosphatase and/or the generation of reactive oxygen species may play an important role in promoting IFn-α-induced apoptosis.
TL;DR: It was concluded that αTC6 cells accumulate l-glutamate in the synaptophysin-containing vesicles in an ATP-dependent manner and secrete it through a Ca 2+ -dependent exocytic mechanism, consistent with the idea that l- glutamate is secreted by α-cells through Ca 2-dependent regulated exocytosis.
Abstract: Pancreatic islet cells express receptors and transporters for L-glutamate and are thus believed to use L-glutamate as an intercellular signaling molecule. However, the mechanism by which L-glutamate appears in the islets is unknown. In the present study, we investigated whether L-glutamate is secreted through exocytosis by alphaTC6 cells (clonal mouse pancreatic alpha-cells). An appreciable amount of L-glutamate was released from cultured cells after the addition of KCl or A23187 in the presence of Ca2+ and 10 mmol/l glucose in the medium. The KCl-induced glutamate release was significantly reduced when assayed in the absence of Ca2+ or when the cells were pretreated with EGTA-AM. The KCl-induced Ca2+-dependent glutamate release was inhibited approximately 40% by voltage-gated Ca2+ channel blockers, such as nifedipine at 20 micromol/l. The degree of KCl-induced Ca2+-dependent glutamate release was correlated with an increase in intracellular [Ca2+], as monitored by fura-2 fluorescence. Botulinum neurotoxin type E inhibited 55% of the KCl-induced Ca2+-dependent glutamate release, followed by specific cleavage of 25 kDa synaptosomal-associated protein. Furthermore, bafilomycin A1, a specific inhibitor of vacuolar H+-ATPase, inhibited 40% of the KCl-induced Ca2+-dependent glutamate release. Immunoelectronmicroscopy with antibodies against synaptophysin, a marker for neuronal synaptic vesicles and endocrine synaptic-like microvesicles, revealed a large number of synaptophysin-positive clear vesicles in cells. Digitonin-permeabilized cells took up L-glutamate only in the presence of MgATP, which is sensitive to bafilomycin A1 or 3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile (a proton conductor) but insensitive to either oligomycin or vanadate. From these results, it was concluded that alphaTC6 cells accumulate L-glutamate in the synaptophysin-containing vesicles in an ATP-dependent manner and secrete it through a Ca2+-dependent exocytic mechanism. The Ca2+-dependent glutamate release was also triggered when cells were transferred in the medium containing 1 mmol/l glucose, suggesting that low glucose treatment stimulates the release of glutamate. Our results are consistent with the idea that L-glutamate is secreted by alpha-cells through Ca2+-dependent regulated exocytosis.
TL;DR: The results indicate that the cellular content of osmotic solutes is enhanced by IAA and reduced by ABA, and it appears that the two plant hormones act on pulvinar motor cells to regulate their turgor pressure, as they do in stomatal guard cells.
Abstract: ;Protoplasts isolated from the laminar pulvinus of Phaseolus vulgaris and bathed in a medium containing KCl as the major salt were found to swell in response to IAA and to shrink in response to ABA. The protoplasts of flexor cells and those of extensor cells responded similarly. The results indicate that the cellular content of osmotic solutes is enhanced by IAA and reduced by ABA. The IAA-induced swelling was abolished when either the K + or the Cl – of the bathing medium was replaced by an impermeant ion or when the medium was adjusted to neutral pH (instead of pH 6). The response was inhibited by vanadate. It is concluded that the swelling is caused by enhanced influxes of K + and Cl – , which probably occur through K + channels and Cl – /H + symporters, respectively. The ABA-induced shrinking was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid, an anion-channel inhibitor, suggesting that it is caused by Cl – efflux through anion channels and chargebalancing K + efflux through outward-rectifying K + channels. It appears that the two plant hormones act on pulvinar motor cells to regulate their turgor pressure, as they do in stomatal guard cells. The findings are discussed in relation to the pulvinar movements induced by environmental stimuli.
TL;DR: Quenching studies with ethanol and tert-butyl alcohol suggest that a monoperoxysulfate radical or a caged sulfate radical are the likely species responsible for oxidation of guanine.
Abstract: Vanadyl sulfate reacts with the peroxy acid oxidant KHSO5 to produce guanine-selective oxidation of a 167-bp restriction fragment of DNA. The oxidized lesions result in strand scission after hot piperidine treatment. Although several reactive intermediates are possible, quenching studies with ethanol and tert-butyl alcohol suggest that a monoperoxysulfate radical or a caged sulfate radical are the likely species responsible for oxidation of guanine. Several oxidants and various vanadium complexes (including insulin mimetic compounds) were studied with DNA for comparison. None of the other vanadium complexes showed modification of the double-stranded 167-bp fragment of DNA in the presence of KHSO5. The reactivity of VOSO4 may be due to its irreversible oxidation potential of 0.77 V (vs. Ag+/AgCl, pH 7.0, 10 mM phosphate), making it an appropriate catalyst for decomposition of monoperoxysulfate.
TL;DR: Computer calculations using X-ray data of known PTPases as a basis for homology modeling then suggests functionality that needs to be addressed in developing selective PTPase inhibitors.
TL;DR: In this paper, NMR and IR spectroscopic studies of the complexes formed between vanadate and the alpha-hydroxylic acid ligands were carried out for aqueous 1 M ionic strength (NaCl) solutions.
Abstract: 51V NMR and IR spectroscopic studies of the complexes formed between vanadate and the alpha-hydroxylic acid ligands, (S)-2-hydroxypropanoic acid (L-(+)-lactic acid), 2-hydroxy-2-methylpropanoic acid, and 2-ethyl-2-hydroxybutanoic acid were carried out for aqueous 1 M ionic strength (NaCl) solutions. Three major products in V to L stoichiometries of 1:1, 2:2, and 3:2 were identified from vanadate and ligand concentration studies, while a pH variation study allowed charge states to be determined. At pH 7.06, the formation constants for the predominant reactions were (26 +/- 1) M (-1), (V + L VL); (6.8 +/- 0.4) x 10(3) M(-1), (2VL V(2)L(2)); and (3.5 +/- 0.3) x 10(3) M(-1), (V(2)L(2) + V V(3)L(2)). Dissolution studies of various crystalline products were carried out for aqueous, nonaqueous, and mixed solvent systems. These studies combined with information available from X-ray structural studies provided a basis for the assignment of solution state structures. Pentacoordinate vanadium in a trigonal-bipyramidal geometry was proposed for the both the 1:1 and 2:2 complexes when in aqueous solution. Observed changes in (51)V chemical shift patterns were consistent with a cis fusion in octahedral coordination for the central vanadium of the 3:2 complex, while the remaining vanadiums retained a pentacoordinate geometry.
TL;DR: Both insulin and vanadate elicit a stimulating effect on GLUT4 gene expression in 3T3-F442A cells, but a prerequisite is that the surrounding glucose concentration is low, suggesting a role of GLUT 4 gene expression for the long-term regulation of cellular insulin action on glucose transport.
TL;DR: A zinc vanadate with the formula Zn3(VO4)2·3H2O was synthesized by hydrothermal reaction of a gel of composition, held at 170°C for 24 hours.
Abstract: A zinc vanadate with the formula Zn3(VO4)2·3H2O was synthesized by hydrothermal reaction of a gel of composition [(CH3CO2)2Zn·2H2O] : 0.5V2O5: 0.4 [1,3-diaminepropane] : 1.5 NaOH : 114 H2O, held at 170°C for 24 hours. The structure was determined ab initio by means of the EXPO direct methods program and refined with GSAS. The pale yellow solid crystallizes in the hexagonal space group P-6 with a= 6.07877(8), c= 7.1827(2) A. The structure consists of vanadium tetrahedra bonded to distorted octahedral zinc atoms to create one dimensional columnar passageways for molecules. Though occupied by water in the as synthesized form, the passages could host other small molecules.
TL;DR: The effect of the Gly263 mutation on the E(1)-E(2) conformational equilibrium seems to be caused mainly by an acceleration of the K(+)-deoccluding step, whereas in the Leu332 mutants the rate of the reverse reaction seems to have been reduced.
Abstract: Gly263 of the rat kidney Na(+),K(+)-ATPase is highly conserved within the family of P-type ATPases. Mutants in which Gly263 or the juxtaposed Arg264 had been replaced by alanine were expressed at high levels in COS-1 cells and characterized functionally. Titrations of Na(+),K(+), ATP, and vanadate dependencies of Na(+),K(+)-ATPase activity showed changes in the apparent affinities relative to wild-type compatible with a displacement of the E(1)-E(2) conformational equilibrium in favor of E(1). The level of the K(+)-occluded form was reduced in the Gly263-->Ala and Arg264-->Ala mutants, and the rate constant characterizing deocclusion of K(+) or Rb(+) was increased as much as 20-fold in the Gly263-->Ala mutant. Studies of the sensitivity of the phosphoenzyme to K(+) and ADP showed a displacement of the E(1)P-E(2)P equilibrium of the phosphoenzyme in favor of E(1)P, and dephosphorylation experiments carried out at 25 degrees C on a millisecond time scale using a quenched-flow technique demonstrated a reduction of the E(1)P to E(2)P conversion rate in the mutants. Hence, the mutations displaced the conformational equilibria of dephosphoenzyme and phosphoenzyme in parallel in favor of the E(1) and E(1)P forms. The observed effects were more pronounced in the Gly263-->Ala mutant compared with the Arg264-->Ala mutant. Leu332 mutations that likewise displaced the conformational equilibria in favor of E(1) and E(1)P were also studied. Unlike the Gly263-->Ala mutant the Leu332 mutants displayed a wild-type like rate of K(+) deocclusion. Thus, the effect of the Gly263 mutation on the E(1)-E(2) conformational equilibrium seems to be caused mainly by an acceleration of the K(+)-deoccluding step, whereas in the Leu332 mutants the rate of the reverse reaction seems to be reduced.
TL;DR: The mechanism of Zn resistance in multiple metal-resistant Pseudomonas putida strain S4 is based on inducible efflux and binding, and the ATPase activity was inhibited by micromolar concentrations of vanadate, suggesting the involvement of a P-type ATPase.
Abstract: The mechanism of Zn resistance in multiple metal-resistant Pseudomonas putida strain S4 is based on inducible efflux. An ATPase in the strain S4 mediated active extrusion of Zn2+, which occurred during the exponential phase of growth. The ATPase activity was inhibited by micromolar concentrations (50 μM) of vanadate, suggesting the involvement of a P-type ATPase. The effluxed Zn2+ were not ejected out of the cell but stored in the outer membrane and periplasm, which provided the required binding sites. The strain S4, thus, employs a dual strategy of efflux and binding to bring about a proper management of essential ions like Zn.
TL;DR: In this article, an aromatic amine template was applied as a structure-directing template for the synthesis of vanadium oxide nanotubes, and a new vanadate has been prepared in high yield by reacting vanadium(V) triisopropoxide and 3-phenylpropylamine in solution, followed by hydrolysis and hydrothermal treatment.
Abstract: A new vanadate has been prepared in high yield by reacting vanadium(V) triisopropoxide and 3-phenylpropylamine in solution, followed by hydrolysis and hydrothermal treatment of the intermediate product. For the first time, an aromatic amine has successfully been applied as structure-directing template for the synthesis of vanadium oxide nanotubes. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images demonstrate the tubular morphology of the phenylpropylamine vanadium oxide nanotubes obtained. The size and structure are similar to that of vanadium oxide nanotubes formed with aliphatic amines. The tube walls comprise layers of vanadium oxide with the organic template intercalated in between. The interlayer distance is ca. 2.1 nm, and the structure of the VOx layers can be described by a square lattice with a≈0.61 nm. Furthermore, the TEM investigation has revealed the presence of many defects in the wall structure.
TL;DR: In this article, the authors demonstrated the direct fabrication of europium doped YVO4 films on vanadium substrate for luminescent materials using hydrothermal-electrochemical method.
TL;DR: It is demonstrated for the first time that TPA‐stimulated MAPK activation is essential for the phosphorylation of several key residues involved in the activation of p70s6K, namely, thr389, thr421, and ser424.
Abstract: The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) triggers cell-cycle progression at G1 phase in mouse embryonic fibroblast C3H 10T1/2 cells was examined TPA treatment resulted in a temporary induction of cyclin D1 peaking at 9 h post stimulation PD98059 (10 μM), the specific inhibitor of MAPK kinase, completely blocked TPA-stimulated cyclin D1 induction and DNA synthesis, confirming that MAPK activation plays an essential role in TPA-stimulated cell-cycle progression Although both PKCα and PKCϵ are expressed in C3H 10T1/2 cells, inhibitor studies suggest that PKCϵ activation is required for the activation of MEK/MAPK signal transduction cascade p70s6K, an important kinase involved in the regulation of protein synthesis and cell-cycle progression, has been reported to be activated through a PKC-dependent pathway (TPA-activatable) in addition to a PI3K-dependent pathway Here, we demonstrate for the first time that TPA-stimulated MAPK activation is essential for the phosphorylation of several key residues involved in the activation of p70s6K, namely, thr389, thr421, and ser424 Vanadate, the tyrosine phosphatase inhibitor, triggered a sustained elevation of the level of active MAPK However, corresponding to a rapid loss of cyclin D1 protein, vanadate treatment resulted in a significant shut out of 3H-thymidine incorporation into DNA regardless of TPA cotreatment Vanadate treatment also led to the increase of active MEK, increased phosphorylation of p70s6K at thr389, thr421, and ser424 yet without activation of PKB These data suggest that vanadate can selectively perturb the activation of signaling components which raises the interesting issue as to how vanadate downregulates the cyclin D1 level © 2001 Wiley-Liss, Inc
TL;DR: In this article, the ac conductivity of several compositions of strontium vanadate semiconducting glasses in the frequency range 10 Hz-2 MHz and in the temperature range 80-450 K was studied.
Abstract: We have studied the ac conductivity of several compositions of strontium vanadate semiconducting glasses in the frequency range 10 Hz-2 MHz and in the temperature range 80-450 K. We have analysed the experimental results in the framework of the quantum tunnelling and classical hopping models. We observe that tunnelling of the overlapping large polarons is the most suitable mechanism for the ac conductivity of the strontium vanadate glasses.
TL;DR: From the results, the generation of energy needed for cell growth from the oxidation of Fe2+ is stopped and the growth inhibition by Na2WO4 observed in A. ferrooxidans is explained as follows: tungsten binds to cytochrome c oxidase in plasma membranes and inhibits cy tochrome c oxidationase activity, and as a results,The generation ofEnergy needed forCell growth is stopped.
Abstract: Cell growth of three hundred iron-oxidizing bacteria isolated from natural environments was inhibited strongly by 0.05 mM, and completely by 0.2 mM of sodium tungstate (Na2WO4), respectively. Since no great difference in the level of tungsten inhibition was observed among the 300 strains tested, the mechanism of inhibition by Na2WO4 was studied with Acidithiobacillus ferrooxidans strain AP19-3. When resting cells of AP19-3 were incubated in 0.1 M beta-alanine-SO4(2-) buffer (pH 3.0) with 0.1 mM Na2WO4 for 1 h, the amount of tungsten bound to the cells was 12 microg/mg protein. The optimum pH for tungsten binding to the resting cells was 2 to approximately 3. Approximately 2 times more tungsten bound to the cells at pH 3.0 than at pH 6.0. The tungsten binding was specifically inhibited by sodium molybdenum. However, copper, nickel, cadmium, zinc, manganese, cobalt, and vanadate did not disturb tungsten binding to the resting cells. The iron-oxidizing activity of AP19-3 was inhibited 24, 62, and 77% by 1, 5, and 10 mM of Na2WO4, respectively. Among the components of iron oxidation enzyme system, iron:cytochrome c oxidoreductase activity was not inhibited by 10 mM of Na2WO4. In contrast, the activity of cytochrome c oxidase purified highly from the strain was inhibited 50 and 72%, respectively, by 0.05 and 0.1 mM of Na2WO4. The amounts of tungsten bound to plasma membrane, cytosol fraction, and a purified cytochrome c oxidase were 8, 0.5, and 191 microg/mg protein, respectively. From the results, the growth inhibition by Na2WO4 observed in A. ferrooxidans is explained as follows: tungsten binds to cytochrome c oxidase in plasma membranes and inhibits cytochrome c oxidase activity, and as a results, the generation of energy needed for cell growth from the oxidation of Fe2+ is stopped.
TL;DR: In cardiomyocytes from lean and obese Zucker rats, both insulin and vanadate stimulate glucose uptake and PKB activation through a PI-3-kinase sensitive pathway and a combination of insulin withVanadate may be beneficial to increase glucose uptake in diabetic hearts, as this gives a better response than insulin alone.
Abstract: Insulin stimulates glucose uptake in muscle cells via activation of protein kinase B (PKB). The protein tyrosine phosphatase (PTP) inhibitor vanadate, is a known insulin mimetic agent but the mechanism whereby vanadate exerts its effect is not clearly understood. Vanadate also has beneficial effects in the diabetic myocardium. The aim of this study was to correlate insulin stimulation of glucose uptake and PKB activation with that induced by vanadate in adult ventricular myocytes from lean and obese Zucker fa/fa rats. In lean Zucker rats, 100 nM insulin and 5 mM vanadate stimulated myocardial 2-deoxy-D-[3H]glucose (2-DG) uptake from 27.17 ± 1.72 to 96.52 ± 10.87 and 43.86 ± 4.02 pmole/mg protein p/30 min respectively while a combination of insulin and vanadate could not improve the maximal response of insulin. In obese Zucker hearts, basal as well as insulin and vanadate stimulated glucose uptake were severely impaired (15.49 ± 1.44 vs 25.51 ± 3.11 and 20.11 ± 1.68 pmole/mg protein/30 min respectively). A combination of insulin and vanadate, resulted in a response significantly improved from the maximal response of insulin. This stimulation of 2-DG uptake was, in all instances, blocked by the PI 3-kinase inhibitors wortmannin and LY 294002. Insulin could not activate PKB, as measured by the Ser473 phosphorylated form of the enzyme, in the obese Zucker rats to the same extent as in lean controls. Similar to glucose uptake, activation of PKB by vanadate plus insulin was significantly more than that accomplished by insulin alone in obese rats. Both insulin and vanadate activation of PKB was prevented by wortmannin and LY 294002. Thus, the present study demonstrates that: (i) in cardiomyocytes from lean and obese Zucker rats, both insulin and vanadate stimulate glucose uptake and PKB activation through a PI-3-kinase sensitive pathway. (ii) In obese Zucker rats, neither insulin nor vanadate could induce glucose uptake or activation of PKB to the same extent as in lean controls. (iii) A combination of insulin with vanadate may be beneficial to increase glucose uptake in diabetic hearts, as this gives a better response than insulin alone.
TL;DR: The ability of vanadate to improve insulin sensitivity clinically may be mediated, at least in part, by its ability to increase Mgi levels, which in turn helps to determine cellular insulin action.
Abstract: The insulin-mimetic effect of vanadate is well established, and vanadate has been shown to improve insulin sensitivity in diabetic rats and humans. Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mg(i)) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mg(i), we utilized (31)P-nuclear magnetic resonance spectroscopy to measure Mg(i) in erythrocytes from normal (NL, n=10) and hypertensive (HTN, n=12) subjects, before and after incubation with insulin and with different doses of sodium vanadate. In NL, vanadate elevated Mg(i) levels, with maximum efficacy at 50 7 micromol/L (186+/-6 to 222+/-6 7micromol/L, P>0.01), as did physiologically maximal doses of insulin, 200 7microU/mL (185+/-6 to 222+/-8 7micromol/L, P<0.01). In HTN, only vanadate, but not insulin, increased Mg(i) (insulin: 173+/-7 to 180+/-9 7micromol/L, P=NS; vanadate: 170+/-7 to 208+/-10 7micromol/L, P<0.01). Mg(i) responses to insulin (r=0.637, P<0.001), but not to vanadate (r=0.15, P=NS), were closely and directly related to basal Mg(i) levels. We conclude that (1) both vanadate and insulin stimulate erythrocyte Mg(i) levels; (2) cellular Mg(i) responses to insulin, but not to vanadate, depend on basal Mg(i) content-the lower the basal Mg(i), the less the Mg(i) response to insulin. As such, (3) Mg(i) responses to vanadate were equivalent among HTN and NL, whereas HTN cells exhibited blunted Mg(i) responses to insulin, and (4) the ability of vanadate to improve insulin sensitivity clinically may be mediated, at least in part, by its ability to increase Mg(i) levels, which in turn, helps to determine cellular insulin action.