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Insights into the molecular mechanism of action of the Anti-Diabetic agent Sodium Tungstate

17 Mar 2010

Speaker: Laura Nocito
Metabolic Engineering and Diabetes Therapy
Molecular Medicine Programme
IRB Barcelona

HOST

Dr. Joan Guinovart, IRB Barcelona

Wednesday, 17 March 2010, 13:00 h, Sala Fèlix Serratosa 

ABSTRACT

The anti-diabetic properties of sodium tungstate have been characterized in several animal models of type 1 and 2 diabetes. In contrast, little is known about the molecular mechanism behind its actions. Our group has shown that the treatment of STZ rats with this compound normalizes glycemia and decreases the expression of several gluconeogenic enzymes, such as PEPCK and G6Pase. We are currently working with primary-cultured rat hepatocytes. Our data show that the treatment with tungstate decreases the expression of several transcription factors involved in this metabolic pathway, while it increases the expression of c-fos, a physiological inhibitor of the transcriptional activity of the PEPCK promoter. Surprisingly, the expression of the SirT-1, a mammalian ortholog of Sir2 (silent information regulator 2) which has been described to stimulate gluconeogenesis, was also increased. However, in our model this increase is not enough to counteract the inhibitory effects of tungstate on gluconeogenesis, maybe due to the lack of PGC-1α, which is also decreased by the treatment. These findings demonstrate that tungstate may exert its action through a mechanism that inhibits gluconeogenesis and leads to a normalization of carbohydrates metabolism.