Effect of vanadium(IV) compounds in the treatment of diabetes: in vivo and in vitro studies with vanadyl sulfate and bis(maltolato)oxovandium(IV)

Willsky, Gail R.; Goldfine, Allison B.; Kostyniak, Paul J.; McNeill, John H.; Yang, Linghui; Khan, H. R.; Crans, Debbie C.

doi:10.1016/s0162-0134(00)00226-9

Cited by 189 publications

(83 citation statements)

References 25 publications

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“…The concentrations of vanadate used in this study are compatible with what has been observed in plasma after chronic treatment with vanadate (50-90 M) in animals and in humans (1,47). This is in contrast to the acute action of this compound, when millimolar concentrations of vanadate are required to produce an effect in vitro (11,19,20,31,41,43).…”

Section: Discussionsupporting

confidence: 80%

“…Vanadium compounds, such as vanadate, are inhibitors of protein tyrosine phosphatases that can mimic a number of the metabolic actions of insulin. In vivo, vanadate lowers blood glucose in diabetic animal models and in humans (5,7,10,31,37,38,47). Oral administration of this compound also restores GLUT4 expression in skeletal muscle of streptozotocin-induced type 1 diabetes (38).…”

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confidence: 99%

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Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Tardif

Julien

Chiasson

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Coderre. Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation. Am J Physiol Endocrinol Metab 284: E1055-E1064, 2003. First published December 10, 2002 10.1152 10. /ajpendo.00134.2002 inhibitor of tyrosine phosphatases, has insulin-mimetic properties. It has been shown that acute vanadate administration enhances glucose uptake independently of phosphatidylinositol (PI) 3-kinase and p38 MAPK. However, therapeutic vanadate use requires chronic administration, and this could potentially involve a different signaling pathway(s). Thus, we examined the mechanisms by which chronic vanadate exposure (16 h) stimulates glucose uptake in primary cultures of adult cardiomyocytes. The effect of vanadate on the activation of insulin-signaling molecules was evaluated 60 min after its withdrawal and in the absence of insulin. We therefore evaluated the persistent effect of vanadate on the insulin-signaling cascade. Our results demonstrate that preincubation with low vanadate concentrations (25-75 M) induces a dose-dependent increase in glucose uptake. The augmentation of this process was not due to alterations in GLUT1 or GLUT4 protein levels, transcription, or de novo protein synthesis. Chronic vanadate exposure was associated with activation of the insulin receptor, insulin receptor substrate-1 (IRS-1), PKB/Akt, and p38 MAPK. Furthermore, inhibition of PI 3-kinase or p38 MAPK by wortmannin and PD-169316, respectively, significantly inhibited vanadate-mediated glucose uptake in cardiomyocytes. Thus, over time, different (albeit overlapping) signaling cascades may be activated by vanadate. insulin signaling; protein kinase B/Akt; diabetes; vanadium; heart; phosphatidylinositol 3-kinase DESPITE THE ABILITY OF THE HEART to use multiple substrates to meet its energy requirements, this organ has one of the highest rates of glucose utilization in vivo (18,45). Decreased glucose uptake has been observed in both type 1 and type 2 diabetic subjects (25,29,45), and it has been proposed that abnormal regulation of this process has a role in the development of cardiac dysfunction (13). In db/db mice, a model of type 2 diabetes characterized by a reduction in glucose utilization and myocardial dysfunction, selective overexpression of the major glucose transporter GLUT4 expressed in the heart normalized these abnormalities (4). Interestingly, vanadate administration to streptozotocin-induced diabetic rats improved both insulin action and myocardial function in these animals (49). Furthermore, it has been shown that chronic vanadate exposure augments glucose uptake and improves ischemic tolerance in the hypertrophied heart (41). Together, these data suggest that glucose is an important cardiac substrate and that vanadate, by stimulating glucose uptake, could have a beneficial effect on the diabetic heart.Vanadium is a trace element found in most cells in concentrations ranging from 0.1 to 1 M (31). Vanadium compounds, such as vanadate, are inhibitors of protein tyrosine...

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Tardif

Julien

Chiasson

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…Among the many vanadium compounds reported in the literature, emphasis is given to the bis(matolato)oxidovanadium(IV) (BMOV) [11,14,37] and the similar one bis(ethylmaltolato) oxidovanadium(IV) (BEOV) [25], the only vanadium compounds tested in clinical trials to date, but other compounds like bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), [VO(dmpp) 2 ] [31,33,[36][37][38][39][40][41], bis(picolinato)oxidovanadium(IV) [VO(pic) 2 ] [24,42,43] and bis(allixinato)oxidovanadium(IV) [18,44,45] have also attracted much interest due to the positive results which have been obtained through in vitro and in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

“…The VO(dmpp) 2 compound has been extensively studied for a structural characterization [30,31] and to investigate its therapeutic properties using adequate cellular models [33,[37][38][39][40]. Recently, it was shown that it is able to restore normal glucose and lipid metabolism in an obese pre-diabetic animal model, the Zucker fatty rats [36].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic properties of VO(dmpp)2 as assessed by in vitro and in vivo studies in type 2 diabetic GK rats

Domingues

Pelletier

Östenson

et al. 2014

Journal of Inorganic Biochemistry

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The bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), VO(dmpp) 2 , has shown anti-diabetic effects by in vitro studies in Wistar (W) rat adipocytes and in vivo in obese Zucker rats. The aim of this work is to confirm the therapeutic properties of VO(dmpp) 2 in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. An in vivo study was carried out, treating W and GK rats during 21 days with a daily dose of VO(dmpp) 2 (44 μmol/kg). It was shown that VO(dmpp) 2 doesn't affect the normal increase of body weight of both W and GK rats, after 8 days of treatment ameliorates glycemia in GK rats (8.4 ± 0.3 vs 10.1 ± 0.2 mM in GK control, P b 0.001) but doesn't interfere with glucose levels in W rats and, after 21 days of treatment, improves the glucose intolerant profile of GK rats (13.1 ± 0.5 vs 20.6 ± 0.7 mM/min in GK control, P b 0.001), despite no increase of plasma insulin levels during glucose tolerance test. Additionally, it was demonstrated that VO(dmpp) 2 significantly enhances [3-3 H]-glucose uptake by W and GK rat adipocytes (non-toxic concentration of 100 μM: respectively 193 ± 20 and 254 ± 21%, P b 0.001, relative to the basal value) showing an efficacy similar to insulin 1.72 nM and better than the same concentration of BMOV (P b 0.01). Western blotting revealed that in W and GK rats VO(dmpp) 2 significantly promotes IRS2 (P b 0.05) and p-AKT expression (P b 0.001 and P b 0.05, respectively, relative to the respective controls) and in GK animals reduces the increase of PTP1β expression (P b 0.001, relative to GK control).

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“…9 A range of vanadium complexes 10 have been synthesized and demonstrated to be effective in lowering hyperglycemia and most importantly, these compounds decrease the side effects of inorganic vanadium salts, possibly by enhancing their rates of absorption in streptozotocin (STZ)-induced diabetic rats. 11 Patients with type 1 or type 2 diabetes had increased renal clearance and fractional excretion of thiamine compared to healthy people. 12 Oral thiamine supplements prevented the development of incipient nephropathy in STZ-induced diabetic rats.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, and efficacy evaluation of a new anti-diabetic vanadyl(II) thiamine hydrochloride complex in streptozotocin-induced diabetic rats

El-Shazly

Ahmed

Ibrahim

et al. 2015

Int J Immunopathol Pharmacol

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Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to abnormalities in either insulin secretion or action. A range of vanadium complexes have been synthesized and demonstrated to be effective in lowering hyperglycemia. Thiamine administration was also reported to prevent deterioration in fasting glucose and insulin levels, and to improve glucose tolerance in hyperglycemic patients. This study has been conducted to evaluate the ionic vanadyl(II) thiamine hydrochloride complex (VC) as a new anti-diabetic candidate. The new complex was characterized by infrared spectroscopy (FT-IR), electronic spectra, magnetic susceptibility, electron spin resonance (ESR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The anti-diabetic effect of VC was investigated in comparison to vanadium sulfate in streptozotocin (STZ)-induced diabetic rats. Treatment of diabetic rats with VC versus vanadyl sulfate showed a more potent effect on reducing serum glucose and cholesterol close to normal levels. VC suppressed the diabetes-induced upregulation of hepatic glucose transporter (GLUT)-2, Phosphoenol pyruvate carboxykinase (PEPCK), and hormone-sensitive lipase (HSL) more significantly than vanadyl sulfate. Either vanadyl sulfate or VC restored hepatic sterol regulatory element-binding protein transcription factor-1c (SREBP-1c) and muscle hexokinase (HK) mRNA expression that was downregulated in diabetic group. Pyruvate kinase (PK) mRNA expression was restored more significantly in VC-treated than vanadyl sulfate-treated diabetic rats. These results indicate that the newly synthesized VC could be an effective anti-diabetic candidate as the anti-diabetic activity of the ionic vanadium was enhanced after being modified with the organic ligand, thiamin. The results also suggest that VC achieves its effect most likely through modulating the transcription of energy metabolizing enzymes.

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Effect of vanadium(IV) compounds in the treatment of diabetes: in vivo and in vitro studies with vanadyl sulfate and bis(maltolato)oxovandium(IV)

Cited by 189 publications

References 25 publications

Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Therapeutic properties of VO(dmpp)2 as assessed by in vitro and in vivo studies in type 2 diabetic GK rats

Synthesis, characterization, and efficacy evaluation of a new anti-diabetic vanadyl(II) thiamine hydrochloride complex in streptozotocin-induced diabetic rats

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