INDUCTION OF INSULIN AND ISLET AMYLOID POLYPEPTIDE PRODUCTION IN PANCREATIC-ISLET GLUCAGONOMA CELLS BY INSULIN PROMOTER FACTOR-1

Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by th e lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (19 94) Nature (London) 371, 606-609]. In adults, IPF1 expression is restr icted to the beta-cells in the islets of Langerhans. We report here th at IPF1 induces expression of a subset of beta-cell-specific genes (in sulin and islet amyloid polypeptide) when ectopically expressed in clo nes of transformed pancreatic islet alpha-cells. In contrast, expressi on of IPF1 in rat embryo fibroblasts factor failed to induce insulin a nd islet amyloid polypeptide expression, This is most likely due to th e lack of at least one other essential insulin gene transcription fact or, the basic helix-loop-helix protein Beta2/NeuroD, which is expresse d in both alpha- and beta-cells. We conclude that IPF1 is a potent tra nscriptional activator of endogenous insulin genes in non-beta islet c ells, which suggests an important role of IPF1 in beta-cell maturation .