The G6pc gene is of particular interest because it was identified as a component of the metformin mechanism in both animal diabetes and in man by nontargeted approaches (11, –, 13) and because G6pc is regulated by the transcription factor ChREBP (14), which is activated by raised cellular phosphorylated intermediates of glucose metabolism in conditions of raised blood glucose or compromised intracellular homeostasis, resulting in raised glucose 6-phosphate, G6P4 (14, –, 17). The gene discussed is G6PC1; the disease is diabetes mellitus.