The AICAR responsive element binding protein (AREBP) suppresses transcription of the gluconeogenic enzyme genes in response to AICAR treatment. Moreover, overexpression of AREBP also suppresses gluconeogenic gene expressions in animals, indicating that AREBP plays an important role in gluconeogenesis. Through a combination of systematic analyses of the AREBP gene promoter and assays for DNA-protein interaction, we identified a nuclear factor involved in tissue-specific expression of AREBP. By targeting this nuclear factor, pharmacological or nutraceutical induction of AREBP gene expression is expected to reduce blood glucose levels in patient with insulin resistance.