Dataset Information

Tungstate reduces the expression of gluconeogenic enzymes in STZ rats.

ABSTRACT:

Aims

Oral administration of sodium tungstate has shown hyperglycemia-reducing activity in several animal models of diabetes. We present new insights into the mechanism of action of tungstate.

Methods

We studied protein expression and phosphorylation in the liver of STZ rats, a type I diabetes model, treated with sodium tungstate in the drinking water (2 mg/ml) and in primary cultured-hepatocytes, through Western blot and Real Time PCR analysis.

Results

Tungstate treatment reduces the expression of gluconeogenic enzymes (PEPCK, G6Pase, and FBPase) and also regulates transcription factors accountable for the control of hepatic metabolism (c-jun, c-fos and PGC1?). Moreover, ERK, p90rsk and GSK3, upstream kinases regulating the expression of c-jun and c-fos, are phosphorylated in response to tungstate. Interestingly, PKB/Akt phosphorylation is not altered by the treatment. Several of these observations were reproduced in isolated rat hepatocytes cultured in the absence of insulin, thereby indicating that those effects of tungstate are insulin-independent.

Conclusions

Here we show that treatment with tungstate restores the phosphorylation state of various signaling proteins and changes the expression pattern of metabolic enzymes.

SUBMITTER: Nocito L

PROVIDER: S-EPMC3414523 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Tungstate reduces the expression of gluconeogenic enzymes in STZ rats.

Nocito Laura L Zafra Delia D Calbó Joaquim J Domínguez Jorge J Guinovart Joan J JJ

PloS one 20120808 8

<h4>Aims</h4>Oral administration of sodium tungstate has shown hyperglycemia-reducing activity in several animal models of diabetes. We present new insights into the mechanism of action of tungstate.<h4>Methods</h4>We studied protein expression and phosphorylation in the liver of STZ rats, a type I diabetes model, treated with sodium tungstate in the drinking water (2 mg/ml) and in primary cultured-hepatocytes, through Western blot and Real Time PCR analysis.<h4>Results</h4>Tungstate treatment r ...[more]

PMID: 22905122

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Project description:Background and Aims: It is well demonstrated that in the beta cell population of the pancreas there is a dynamic turnover, which results from the net balance of several processes; beta cell replication, apoptosis and neogenesis. These processes have been studied in partial pancreatectomy and glucagon-like peptide 1 treated animals, where an increase in pancreas regeneration has been observed. Similarly, sodium tungstate, which decreases hyperglycemia in several animal models of diabetes, promotes a rise in the beta cell mass of nSTZ and STZ animals. However, the molecular mechanisms underlying this pancreas regeneration remain unknown. Therefore the objective of this study is to identify which genes are up or down regulated in the increase of the beta cell population of STZ rats treated with sodium tungstate. Materials and methods: Adult male Wistar (225-250 g) rats were kept under a constant 12-hour light-dark cycle and rats were kept under a constant 12-hour light-dark cycle and were allowed to eat and drink freely. Diabetes was induced by a single i.p. injection of streptozotocin (STZ) (70 mg/Kg body weight) in 0.9% NaCl with 100 mmol/L sodium citrate buffer (pH 4.5). Diabetes was confirmed by determination of its hyperglycaemia (>500mg/dL [Reflotron, Roche Diagnostic]). Healthy rats received an i.p. injection of the vehicle. Treatment started 7 days after the STZ or vehicle injection. Diabetic and healthy rats were divided into two groups. In the first (untreated), rats received deionized drinking water; in the second (treated) group, they were given a solution of sodium tungstate. During the first week of treatment, the rats received a solution of 0.7 mg/mL and in the next 4-5 weeks, the concentration was increased to 2 mg/mL. At the end of the experiment, the animals were sacrificed and pancreatic RNA isolated. Three chips (Affymetrix RAE-230A) were hybridized for each of the four experimental groups (untreated and treated healthy rats and untreated and treated diabetic rats). The raw intensity data obtained from the microarrays was normalized and summarized using the Bioconductor package RMA. Keywords = pancreas regeneration Keywords = STZ Keywords = diabetes Keywords = tungstate Keywords = insulin-like agents Keywords = beta cell plasticity Keywords = neogenesis Keywords: ordered

Dataset Information

Tungstate reduces the expression of gluconeogenic enzymes in STZ rats.

Aims

Methods

Results

Conclusions

Publications

Tungstate reduces the expression of gluconeogenic enzymes in STZ rats.

Similar Datasets

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