Figure 7.Regulation of TXNIP through the glycolitic pathway and its modulation by limited glucose availability (LGA), resveratrol and DHEA. Down regulation
of glucose levels is known to increase the AMP/ATP ratio which in turn
activates AMPK, leading to increased serine phosphorylation of ChREBP.
Phosphorylated ChREBP is unable to translocate into the nucleus and form a
functional complex with Mlx that is required for TXNIP expression. In
addition, reduced glucose levels would inhibit, the pentose pathway and
lead to the inhibition of the phosphatase PP2A. This will also result in
the accumulation of phosphorylated ChREBP in the cytoplasm and further
inhibition of TXNIP expression. DHEA acts on this glycolytic pathway mainly
through the inhibition of G6PD activity. Resveratrol would act through the
induction of Sirt1-mediated phosphorylation of AMPK, leading to enhanced
phosphorylation ChREBP and inhibition of its nuclear translocation. This
mechanism sheds light on TXNIP as a common downstream target for putative
anti-aging interventions that affect metabolism.
