Organo-vanadium compounds are potent activators of the protein kinase B signaling pathway and protein tyrosine phosphorylation: Mechanism of insulinomimesis

Mehdi, Mohamad Z.; Srivastava, Ashok K.

doi:10.1016/j.abb.2005.06.008

Cited by 42 publications

(39 citation statements)

References 48 publications

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“…Moreover, BMOV-induced enhanced PKB phosphorylation required PI3-K, since pharmacological blockade of PI3-K with wortmannin in CHO cells overexpressing IR almost completely abrogated the BMOV response (Fig. 3) (22). In addition to BMOV, other OVCs, such as bis(acetylacetonato)-oxovanadium (IV), bis(picolinate)-oxovanadium (IV), bis(3-methylpicolinato) -oxovanadium (IV), bis(6-methylpicolinato) -oxovanadium (IV), and bis(allixinato)-oxovanadium (IV) (VO(alx) 2 ), were also shown to induce the Ser 473 phosphorylation of PKB in 3T3-L1 adipocytes (22,(68)(69)(70).…”

Section: Bmov Activates Pkb Phosphorylationmentioning

confidence: 99%

“…higher PTPase inhibitory potential of the OVC was associated with more robust tyrosine phosphorylation of several proteins, including the IR-ß and IRS-1 (22,65), and was associated with activation of several components of the insulin signaling pathways (66)(67)(68)(69)(70) (Fig. 1).…”

Section: Bmov Protein Tyrosine Phosphatases (Ptpases) and Insulin Simentioning

confidence: 99%

“…3) (22). In addition to BMOV, other OVCs, such as bis(acetylacetonato)-oxovanadium (IV), bis(picolinate)-oxovanadium (IV), bis(3-methylpicolinato) -oxovanadium (IV), bis(6-methylpicolinato) -oxovanadium (IV), and bis(allixinato)-oxovanadium (IV) (VO(alx) 2 ), were also shown to induce the Ser 473 phosphorylation of PKB in 3T3-L1 adipocytes (22,(68)(69)(70). In fact, recent studies showed that daily oral administration of VO(alx) 2 enhanced PKB and GSK-3 phosphorylation and decreased elevated blood glucose levels in a streptozotocin (STZ)-induced diabetic mouse model (70), suggesting that PKB phosphorylation is a key step in the regulation of glucose homeostasis in response to OVCs (70).…”

Section: Bmov Activates Pkb Phosphorylationmentioning

confidence: 99%

“…It was also shown that in vivo therapy of diabetic rodents with various vanadium compounds (60)(61)(62), as well as in vitro vanadium treatment of hepatocytes (63) and hepatoma cells (64) inhibited the activity of multiple PTPases, such as SH2 domain-containing PTPase (SHP2) (63), PTP1B (62,65) and total PTPase (22,60,61,63,64). Furthermore, as compared to inorganic vanadium salts, organo-vanadium compounds (OVC), such as BMOV and VAC, have been shown to be more potent than VS in inhibiting PTP activity (22). This Upon insulin binding to the extracellular ·-subunits of the IR, a conformational modification of the ß-subunits occurs, resulting in its autophosphorylation on several tyrosine residues.…”

Section: Bmov Protein Tyrosine Phosphatases (Ptpases) and Insulin Simentioning

confidence: 99%

“…Encouraged by better tolerance of BMOV, several OVCs have been synthesised and tested for their ability to exert insulin-like effects. These include vanadium (IV) oxo bis (acetylacetonate) (VO(acac) 2 /VAC) (22), vanadium (IV) oxo bis (3-ethylacetylacetone) (VET), vanadium (IV) oxo bis (ethylmaltolato) (BEOV), vanadium (IV) oxo bis (6-methylpicolinato), and L-glutamic acid ‰-monohydroxamate-NaOV complex (23-31). These OVC have been shown to be better absorbed and less toxic than inorganic salts and exhibit a much higher glucose lowering effect in animal models of diabetes as compared to inorganic vanadium salts (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

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Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes toits glucoregulatory responses (Review)

Vardatsikos

Mehdi²,

Srivastava³

2009

Int J Mol Med

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Abstract. Over the last several decades, a large body of evidence has accumulated to suggest that organo-vanadium compounds (OVC) are more potent than inorganic vanadium salts in regulating hyperglycemia and insulin-resistance in rodent models of both type I and type II diabetes. Among these OVC, vanadium (IV) oxo bis(maltolato) (BMOV) was the first to be investigated for its higher potency over inorganic vanadium salts in eliciting insulin-like properties in both in vitro and in vivo systems. While the precise molecular mechanism by which BMOV exerts its insulin-mimetic effects remains poorly defined, studies have shown that BMOV is a potent activator of several key components of the insulin signaling pathways, such as phosphatidyl-inositol 3-kinase (PI3-K), and its downstream effector, protein kinase B (PKB). In addition, BMOV-induced phosphorylation of PKB has also been associated with the enhanced phosphorylation of glycogen synthase kinase-3 (GSK-3) and forkhead box protein 1 (FOXO1). Since PKB is instrumental in mediating the effects of insulin on glucose transport, glycogen synthesis and gluconeogenesis, it is reasonable to suggest that activation of this pathway by BMOV serves as a mechanism for its insulin-like effects. Contents1. Introduction 2. The insulin signaling pathway 3. BMOV, protein tyrosine phosphatases (PTPases) and insulin signaling 4. BMOV activates PKB phosphorylation 5. BMOV enhances phosphorylation of GSK-3 6. BMOV enhances phosphorylation of FOXO1 7. BMOV and IR phosphorylation 8. Conclusions IntroductionRecent decades have witnessed a dramatic surge in the incidence of diabetes, and according to the estimates of the World Health Organization (WHO), about 180 million people worldwide currently have this disease, which may double by 2030 (1). Diabetes is caused by an absolute or relative lack of insulin secretion or action. Insulin is a polypeptide hormone, synthesized and secreted by the ß-cells of the pancreas, which regulates carbohydrate metabolism. Two major forms of diabetes are: type 1, formerly known as insulin-dependent diabetes mellitus, and type 2, that is, noninsulin-dependent diabetes mellitus. In type 1 diabetes, the absolute lack of insulin secretion is due primarily to the destruction of ß-cells by autoimmune mechanisms. On the other hand, in type 2 diabetes, ß-cells are able to produce insulin, but their insulin secretory response and insulin action on target tissues are defective. About 90% of the total diabetic population falls into the type 2 category, while the remaining 10% are type 1. Type 2 diabetes may be treated by diet control and/or by oral hypoglycemic agents, such as sulfonylurea, biguanides and thiazolidinediones. However, type 1 diabetics require regular daily injections of insulin to treat their diabetes, as well as some type 2 diabetics in the advanced stage of the disease. Although the availability of highly-purified insulin and the use of oral hypoglycemic drugs as monotherapy or in combination with other agents have greatly improved the management of...

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Section: Bmov Activates Pkb Phosphorylationmentioning

confidence: 99%

Section: Bmov Protein Tyrosine Phosphatases (Ptpases) and Insulin Simentioning

confidence: 99%

Section: Bmov Activates Pkb Phosphorylationmentioning

confidence: 99%

Section: Bmov Protein Tyrosine Phosphatases (Ptpases) and Insulin Simentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes toits glucoregulatory responses (Review)

Vardatsikos

Mehdi²,

Srivastava³

2009

Int J Mol Med

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Interaction of [V^IVO(acac)₂] with Human Serum Transferrin and Albumin

Correia

Chorna

Cavaco

et al. 2017

Chemistry An Asian Journal

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[VO(acac) ] is a remarkable vanadium compound and has potential as a therapeutic drug. It is important to clarify how it is transported in blood, but the reports addressing its binding to serum proteins have been contradictory. We use several spectroscopic and mass spectrometric techniques (ESI and MALDI-TOF), small-angle X-ray scattering and size exclusion chromatography (SEC) to characterize solutions containing [VO(acac) ] and either human serum apotransferrin (apoHTF) or albumin (HSA). DFT and modeling protein calculations are carried out to disclose the type of binding to apoHTF. The measured circular dichroism spectra, SEC and MALDI-TOF data clearly prove that at least two VO-acac moieties may bind to apoHTF, most probably forming [V O(acac)(apoHTF)] complexes with residues of the HTF binding sites. No indication of binding of [VO(acac) ] to HSA is obtained. We conclude that V O-acac species may be transported in blood by transferrin. At very low complex concentrations speciation calculations suggest that [(VO)(apoHTF)] species form.

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On the Fate of Vanadate in Human Blood

2006

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As a summary of recent activities at our research group, a model describing the distribution of pentavalent vanadium (referred to as vanadate throughout the present work) in human blood has been constructed based on our speciation studies performed in the physiological medium of 0.150 M Na(Cl) with various blood constituents. In addition, other data (most notably with the high mass serum constituents albumin and transferrin) have also been used to give as broad a view as possible. Two antidiabetic drug candidate ligands, picolinate and maltol, have also been included in order to investigate the stability of their vanadium complexes in the presence of blood constituents, i.e. to account for ligand‐exchange possibilities. The model predicts transferrin to be the major carrier of vanadium in the bloodstream. It is capable of almost completely replacing the vanadium‐bound picolinate even if the latter is in large excess. Maltol, on the other hand, can retain most of the vanadium when it is supplied in about a 5 mM concentration. The model still has certain limitations but it serves as a useful base for investigating structure, stability, relationship effects and provides insight into the fate of vanadate in human blood.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Organo-vanadium compounds are potent activators of the protein kinase B signaling pathway and protein tyrosine phosphorylation: Mechanism of insulinomimesis

Cited by 42 publications

References 48 publications

Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes toits glucoregulatory responses (Review)

Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes toits glucoregulatory responses (Review)

Interaction of [V^IVO(acac)₂] with Human Serum Transferrin and Albumin

On the Fate of Vanadate in Human Blood

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Organo-vanadium compounds are potent activators of the protein kinase B signaling pathway and protein tyrosine phosphorylation: Mechanism of insulinomimesis

Cited by 42 publications

References 48 publications

Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes toits glucoregulatory responses (Review)

Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes toits glucoregulatory responses (Review)

Interaction of [VIVO(acac)2] with Human Serum Transferrin and Albumin

On the Fate of Vanadate in Human Blood

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Interaction of [V^IVO(acac)₂] with Human Serum Transferrin and Albumin