Decreased DNA binding of another important transcription factor, RIPE-3b1 activator, also appeared to be involved (8,10), which may explain why transfection of PDX-1 cDNA alone was not sufficient for complete restoration of insulin promoter activity (9). We extended this work to an in vivo model, the ZDF rat, and observed that these animals lost islet DNA binding activity of PDX-1 as well as insulin gene expression as they progressively developed more severe hyperglycemia (11).