The system is extremely sensitive, and is particularly suited for this purpose, because it excludes the effects of glucose on nuclear entry and DNA binding activity of ChREBP and focuses on the transcrip- tional activation itself [15]. We found that inhibition of hexokinase by D-mannoheptulose completely shuts down transactivation of ChREBP (Fig. 1A), suggesting that this second pathway is also dependent on the metabolism of glucose.