We propose that the ALX3-dependent stimulation of the oxidative stress defence response is mediated by an indirect transcriptional activation pathway involving Foxo1, because we did not find DNA sequence motifs corresponding to putative ALX3 binding sites in the promoter regions of any of the target genes examined. Taken together, all these data support the proposal that high glucose concentrations favouring the generation of oxidative stress stimulate the expression of Alx3, which in turn activates the expression of Foxo1, thus stimulating the expression of the genes encoding ROS scavenging enzymes47, 48.