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. 

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