Administration of the PPARα ligand fenofibrate to mice caused decreased expression levels of glucokinase as well as a decreased flux through this enzyme, indicative of lower hepatic glucose uptake [30]. Decreased transcripts of PK [30–33] and decreased glucokinase activity [31] after administration of an exogenous PPARα ligand, suggested that PPARα indeed controls the glycolytic pathway (Figure 2). In contrast, in other studies, glucokinase expression was not affected by feeding mice the PPARα activator WY14643 [7]. The rat glucokinase promoter contains a functional PPAR response element (PPRE) [34], which was shown to be activated both by LXRα/RXRα and PPARγ/RXRα in a luciferase reporter assay [26]. Interaction of this PPRE with PPARα, however, was not studied so far.
