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PLoS By Category | Recent PLoS Articles
Biochemistry - Diabetes and Endocrinology - Molecular Biology

Tungstate Reduces the Expression of Gluconeogenic Enzymes in STZ Rats
Published: Wednesday, August 08, 2012
Author: Laura Nocito et al.

by Laura Nocito, Delia Zafra, Joaquim Calbó, Jorge Domínguez, Joan J. Guinovart

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 PGC1a). 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.

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