Previous work has addressed one aspect of activation of ChRE- BP, i.e., xylulose-5-phosphate mediated nuclear entry and DNA binding [12,13]. However, the signaling pathway that leads to the other aspect of ChREBP activation, i.e., turning on its transcrip- tional activity, remains unknown. We have previously shown that high glucose-induced activation exists in cells and tissues where the pentose-phosphate pathway is almost non-existent [10], impli- cating the involvement of signaling molecules other than xylulose- 5-phosphate. In this study, we focused our attention on the transcription activation of ChREBP using the GAL4-ChREBP system.