Vanadate inhibits glucose output from isolated perfused rat liver

Bruck, Rafael; Prigozin, Haia; Krepel, Z.; Rotenberg, P; Shechter, Yoram; Bar‐Meir, Simon

doi:10.1002/hep.1840140322

Cited by 26 publications

(7 citation statements)

References 37 publications

(18 reference statements)

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“…These results are compatible with previous studies in the IPRL, that reported insulin extraction of 40-50% (Mondon et al 1975). The addition of vanadate in low concentrations (1 uM), that effectively blocked hepatic glucose production in the same experimental model (Bruck et al 1991), had no effect on insulin extraction that decreased to 42+2% (p = 0.12, Table 1). Similar results were obtained with 5 uM vanadate (Fig.…”

Section: Effect Of Vanadate On Insulin Extractionsupporting

confidence: 92%

“…Insulin binding to its receptor may affect receptor as well as post-receptor insulin dependent events. In order to test this hypothesis, we used vanadate in low concentrations that were shown to effectively inhibit glucose output from the isolated perfused rat liver (1-5 uM) (Bruck et al 1991). The lack of effect of vanadate on insulin extraction observed in the present study, essentially excludes the possibility of altered insulin degradation as a mechanism by which vanadate exerts its insulin-like effects.…”

Section: Discussionmentioning

confidence: 77%

“…Several studies have shown that vanadate ions mimic insulin action in isolated adipocytes by a post-receptor mechanism (Shechter, Amir and Meyerovitz 1988;Shechter 1990). Administration of vanadate in drinking water normalizes blood glucose levels in streptozotocin-treated diabetic rats {Meyerovitz, Farfel, Sack and Shechter 1987), and recently it has been shown that very low doses of vanadate (1-5 uM) effectively inhibit glucose production by the isolated perfused rat liver (IPRL) {Bruck, Prigozin, Krepel, Rotenberg, Shechter and Bar-Meir 1991). The mechanism(s) responsible for the insulin-like effects of vanadate are still unclear and several possible explanations have been raised (Shisheva and Shechter 1992).…”

Section: Introductionmentioning

confidence: 99%

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Vanadate Has no Effect on Insulin-Extraction by the Rat Liver

Bruck

Melzer²,

Karasik³

et al. 1994

Horm Metab Res

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The mechanism(s) responsible for the insulin-like effects of vanadate are still unclear, although several possible explanations have been raised. However, the possibility that vanadate induces inhibition of insulin degradation in the liver was not examined yet. Therefore, in the present study we examined the effect of vanadate on the extraction of insulin by the perfused rat liver using an open, non-recycling system. Baseline insulin extraction (44 +/- 2% and 37 +/- 3%) was not affected by the administration of 1 and 5 microM vanadate (decreased to 42 +/- 2% and 36 +/- 1, respectively, p = NS). Vanadate had no adverse effects on liver viability, and the bile flow remained stable during and after vanadate administration (0.87 +/- 0.08 microliter/min/g liver prior to Vs. 0.084 +/- 0.11 microliter/min/g liver following vanadate administration). This study shows that vanadate does not inhibit insulin extraction by the perfused liver, and that does of vanadate that effectively inhibit hepatic glucose production possess no adverse effects on liver viability.

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Section: Effect Of Vanadate On Insulin Extractionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vanadate Has no Effect on Insulin-Extraction by the Rat Liver

Bruck

Melzer²,

Karasik³

et al. 1994

Horm Metab Res

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“…The reason for these discrepant findings is not clear, but the type of model, duration of therapy, and vanadium dose are potentially relevant. An inhibitory action of NaMV on glucose output has been documented in isolated, perfused rat livers [91], and Vac can suppress gluconeogenesis in isolated hepatocytes and kidney cortex tubules from control and diabetic rabbits [92]. Consistent with these data on gluconeogenesis, vanadium treatment decreased the heightened expression of the gluconeogenic enzymes PEPCK and G6Pase [93–99].…”

Section: Effect On Gluconeogenesismentioning

confidence: 78%

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

2004

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Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes.

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“…Thus, a number of studies used the rat as donor species in a model of isolated perfused livers to examine drugand chemical-induced hepatotoxicity. Using this model, numerous compounds were examined including insecticides such as lindane or mirex (31), aliphatic alcohols (29), antibiotic agents such as nitrofurantoin (28), solvents such as dimethylacetamide (24), aromatic amines (5), or metals such as cadmium, copper, vanadium, or aluminum (6,32). However, as the rat liver displays signi cant differences in organ size and geometry as compared to human livers, the pig livers used display a better approach to simulating human in vivo conditions.…”

Section: Discussionmentioning

confidence: 99%

Isolated Hemoperfused Slaughterhouse Livers as a Valid Model to Study Hepatotoxicity

et al. 2002

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Different models of isolated and perfused livers and precision cut liver slices have been developed for studies on liver toxicology the past years. As most of these models were limited by nonphysiologic settings, a new model of normothermic hemoperfused isolated porcine slaughterhouse livers to examine hepatotoxicity was established encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. As model compound, the analgesic substance diclofenac was used and the effects of this drug on organ function parameters were compared to an untreated control group. Using an amount of 2,000 ml, the organs were perfused over 180 minutes, metabolically controlled via a dialysis and oxygenation system and various hematological and hepatic parameters were examined. In contrast to the untreated control organs, significant differences were found in the diclofenac group for parameters such as lactate, creatinine, ALT, bicarbonate, or bile flow. In summary, the presently established model of isolated hemoperfused slaughterhouse livers displays a useful new approach to assess hepatotoxicity of different substances on the organ level. As a major economic advantage in comparison to setups using laboratory animals, the new model can be run with blood and organs obtained from slaughterhouse animals.

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Vanadate inhibits glucose output from isolated perfused rat liver

Cited by 26 publications

References 37 publications

Vanadate Has no Effect on Insulin-Extraction by the Rat Liver

Vanadate Has no Effect on Insulin-Extraction by the Rat Liver

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

Isolated Hemoperfused Slaughterhouse Livers as a Valid Model to Study Hepatotoxicity

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