Mechanism of insulin sensitization by BMOV (bis maltolato oxo vanadium); unliganded vanadium (VO4) as the active component

Peters, Kevin G.; Davis, Mike G.; Howard, Brian W.; Pokross, Matthew; Rastogi, Vinit K.; Diven, Conrad; Greis, Kenneth D.; Eby-Wilkens, Elaine; Maier, Matthew; Evdokimov, A.G.; Soper, Shari; Genbauffe, Frank

doi:10.1016/s0162-0134(03)00236-8

Cited by 132 publications

(125 citation statements)

References 66 publications

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“…Consequently, glucose-uptake is related to the inhibition of FFA-release from isolated rat adipocytes treated with epinephrine. 28,29,48) Vanadium compounds are considered to activate IRS, 49) PI3-K, 50) GLUT-4, 51,52) cyclic nucleotide phosphodiesterases (PDEs), 53) and protein tyrosine phosphatases (PTPs), 54,55) analogous with the action of insulin. While, vanadyl ions inhibit FFA-release from adipocytes treated with epinephrine.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

Adachi

Sakurai

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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We have recently proposed the existence of some potent vanadyl complexes with blood glucose-lowering activity in experimental diabetic animals based on the results of an in vitro FFA (free fatty acids)-release assay in isolated rat adipocytes treated with epinephrine and evidence of an in vivo blood glucose lowering effect in experimental diabetic animals. However, the FFA assay depends indirectly on the glucose-uptake of vanadyl complexes in adipocytes. It is therefore necessary to develop a more reliable in vitro glucose-uptake assay, in place of the glucose uptake method using radioactive compounds such as 14 C-glucose, to identify insulin-mimetic vanadyl complexes. In the present study, we proposed a combined in vitro assay by using the conventional glucose oxidase method for glucose-uptake and FFA assay in isolated rat adipocytes. Insulin, vanadyl sulfate (VOSO 4 ), bis(picolinato)vanadyl (VO(pa) 2 ), and bis(6-methylpicolinato)vanadyl (VO(6mpa) 2 ) complexes exhibited concentration-dependent uptake of (؉)-D-glucose and inhibition of FFA release in the adipocytes treated with epinephrine. Vanadyl complexes were found to accelerate glucose-uptake at lower concentrations than VOSO 4 . In vitro high insulin-mimetic activity of VO(pa) 2 and VO(6mpa) 2 were thus indicated by both glucose-uptake and FFA-release, with the insulin-mimetic activity of VO(6mpa) 2 being higher than that of VO(pa) 2 , as suggested by the partition coefficient (0.330 for VO(pa) 2 and 0.595 for VO(6mpa) 2 ). The proposed assay provides a more reliable method than each single method for the evaluation of in vitro insulin-mimetic activity of compounds.Key words vanadyl compound; glucose-uptake assay; free fatty acids (FFA)-release assay; insulin-mimetic effect; adipocyte 428

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Section: Discussionmentioning

confidence: 99%

Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

Adachi

Sakurai

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…A kinetic assay was performed using a 0.1% Triton-X100 osteoblast extract and the fluorogenic small substrate 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) (Peters et al, 2003). The cell extract was incubated with 10 mM DiFMUP in phosphate buffer, pH 7.0, for 15 min.…”

Section: Phosphatase Assaymentioning

confidence: 99%

Osteogenic activity of vanadyl(IV)–ascorbate complex: Evaluation of its mechanism of action

Cortizo

Molinuevo

Barrio

et al. 2006

The International Journal of Biochemistry & Cell Biology

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We have previously shown that different vanadium(IV) complexes regulate osteoblastic growth. Since vanadium compounds are accumulated in vivo in bone, they may affect bone turnover. The development of vanadium complexes with different ligands could be an alternative strategy of use in skeletal tissue engineering. In this study, we have investigated the osteogenic properties of a vanadyl(IV)-ascorbate (VOAsc) complex, as well as its possible mechanisms of action, on two osteoblastic cell lines in culture. VOAsc (2.5-25 mM) significantly stimulated osteoblastic proliferation (113-125% basal, p < 0.01) in UMR106 cells, but not in the MC3T3E1 cell line. VOAsc (5-100 mM) dose-dependently stimulated type-I collagen production (107-156% basal) in osteoblasts. After 3 weeks of culture, 5-25 mM VOAsc increased the formation of nodules of mineralization in MC3T3E1 cells (7.7-20-fold control, p < 0.001). VOAsc (50-100 mM) significantly stimulated apoptosis in both cell lines (170-230% basal, p < 0.02-0.002), but did not affect reactive oxygen species production. The complex inhibited alkaline and neutral phosphatases from osteoblastic extracts with semi-maximal effect at 10 mM doses. VOAsc induced the activation and redistribution of P-ERK in a time-and dose-dependent manner. Inhibitors of the mitogen activated protein kinases (MAPK) pathway (PD98059 and UO126) partially blocked the VOAsc-enhanced osteoblastic proliferation and collagen production. In addition, wortmanin, a PI-3-K inhibitor and type-L channel blocker nifedipine also partially abrogated these effects of VOAsc on osteoblasts. Our in vitro results suggest that this vanadyl(IV)-ascorbate complex could be a useful pharmacological tool for bone tissue regeneration. © 2005 Elsevier Ltd. All rights reserved.

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“…Furthermore, the impact of the broad spectrum pan‐PTP inhibitor BMOV, previously only analysed in diabetic rats 31, was explored. BMOV is characterized by a nonselective inhibition of different PTPs 32, including PTP1B 33. Metabolic phenotyping – body weight, ITT, GTT – revealed in both pharmacological groups a beneficially altered metabolic status in HFD‐induced insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Src homology 2 domain‐containing phosphatase 1 increases insulin sensitivity in high‐fat diet‐induced insulin‐resistant mice

et al. 2016

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Insulin resistance plays a crucial role in the development of type 2 diabetes. Insulin receptor signalling is antagonized and tightly controlled by protein tyrosine phosphatases (PTPs). However, the precise role of the PTP src homology 2 domain‐containing phosphatase 1 (SHP‐1) in insulin resistance has not been explored. Male C57BL/6J mice were fed a high‐fat diet (HFD, 60% kcal from fat), to induce insulin resistance, or a low‐fat diet (LFD, 10% kcal from fat) for 10 weeks. Afterwards, HFD‐fed mice were pharmacologically treated with the SHP‐1 (Ptpn6) inhibitor sodium stibogluconate and the broad spectrum pan‐PTP inhibitor bis(maltolato)oxovanadium(IV) (BMOV). Both inhibitors ameliorated the metabolic phenotype, as evidenced by reduced body weight, improved insulin sensitivity and glucose tolerance, which was not due to altered PTP gene expression. In parallel, phosphorylation of the insulin receptor and of the insulin signalling key intermediate Akt was enhanced, and both PTP inhibitors and siRNA‐mediated SHP‐1 downregulation resulted in an increased glucose uptake in vitro. Finally, recombinant SHP‐1 was capable of dephosphorylating the ligand‐induced tyrosine‐phosphorylated insulin receptor. These results indicate a central role of SHP‐1 in insulin signalling during obesity, and SHP‐1 inhibition as a potential therapeutic approach in metabolic diseases.

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Mechanism of insulin sensitization by BMOV (bis maltolato oxo vanadium); unliganded vanadium (VO4) as the active component

Cited by 132 publications

References 66 publications

Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

Osteogenic activity of vanadyl(IV)–ascorbate complex: Evaluation of its mechanism of action

Inhibition of Src homology 2 domain‐containing phosphatase 1 increases insulin sensitivity in high‐fat diet‐induced insulin‐resistant mice

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