Regulation of the insulin gene by glucose: stimulation of trans-activation potency of human PDX-1 N-terminal domain

DNA Cell Biol. 1999 Jun;18(6):471-9. doi: 10.1089/104454999315196.


The beta cells in pancreatic islets of Langerhans increase insulin gene transcription in response to glucose. The pancreatic and duodenal homeobox-1 (PDX-1) plays a major role in glucose-induced insulin transcription. We studied the functional regions of the human PDX-1 protein fused to the DNA-binding domain of the transcription factor Gal4. The results indicate that the N-terminal domain of the hPDX-1, required for transactivation (amino acids 1-120) in transfected betaTC6 and HeLa cells, is also regulated by extracellular glucose concentrations in transfected rat islets. Deletion analyses have led to the mapping of two regions within the N terminus that are essential for its trans-activation properties. One sequence spans amino acids 97-120 in transfected islet and HeLa cells or amino acids 77-120 in betaTC6 cells; the other includes the highly conserved B box (amino acids 31-41). We thus present evidence of a glucose effect on hPDX-1 trans-activation activity, in addition to the previously described regulatory effect on its DNA-binding activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins
  • Fungal Proteins / genetics
  • Gene Expression Regulation* / drug effects
  • Glucose / physiology*
  • HeLa Cells
  • Homeodomain Proteins*
  • Humans
  • Insulin / genetics*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Male
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / genetics
  • Saccharomyces cerevisiae Proteins*
  • Structure-Activity Relationship
  • Trans-Activators / genetics*
  • Transcription Factors / genetics
  • Transfection
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • Homeodomain Proteins
  • Insulin
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein
  • Glucose