In the adult pancreas the expression of the transcription factor PDX1 is mainly restricted to the beta-cells of the islets of Langerhans. In this study we have identified a region of the pdx1 promoter between -2715 and -1960 which was essential to direct pancreatic islet-cell-specific expression of PDX1. We have also begun for the first time to understand the complex nutritional and hormonal regulation controlling PDX1 expression. The current study has established the fact that glucose, GLP-1, insulin, T-3, HB-EGF, and TNF-alpha. all positively regulate the PDX1 gene promoter in pancreatic beta-cells. This study represents the first detailed exploration of the nutritional and hormonal regulation of this vital beta-cell gene. (C) 2002 Elsevier Science (USA). All rights reserved.