Figure 1.

Metabolite-mediated activation of ChREBP-α and induction of ChREBP-β. Substrates that raise cellular levels of hexose-phosphates (C₆P) and triose-phosphates (C₃P) cause translocation of full-length ChREBP-α from the cytoplasm to the nucleus and binding to upstream (ChREBP-β) and downstream (ChREBP-α) ChoREs of the ChREBP gene and to ChoREs of various ChREBP target genes G6pc, Pklr, and Gckr. ChREBP-β which unlike ChREBP-α is present constitutively in the nucleus exerts positive feedback on its own promoter but negative feedback on the downstream ChREBP-α promoter. This accounts for the modest changes in ChREBP-α mRNA levels in comparison with ChREBP-β mRNA during high glucose activation.