Carbohydrate responsive element-binding protein (ChREBP) is a transcription factor whose expression and activity are increased in pancreatic beta-cells maintained at elevated glucose concentrations. We show here that ChREBP inactivation in clonal pancreatic MIN6 beta-cells results in an increase in Pdx-1 expression at low glucose and to a small, but significant, increase in Ins2, GcK and MafA gene expression at high glucose concentrations. Conversely, adenovirus-mediated over-expression of ChREBP in mouse pancreatic islets results in decreases in Pdx-1, MafA, Ins1, Ins2 and GcK mRNA levels. These data suggest that strategies to reduce ChREBP activity might protect against beta-cell dysfunction in type 2 diabetes. (C) 2010 Elsevier Inc. All rights reserved.