Diabetologia

, Volume 45, Issue 3, pp 309–326

Regulation of insulin gene transcription

Authors

  • D. Melloul
    • Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem, Israel
  • S. Marshak
    • Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem, Israel
  • E. Cerasi
    • Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem, Israel
Review

DOI: 10.1007/s00125-001-0728-y

Cite this article as:
Melloul, D., Marshak, S. & Cerasi, E. Diabetologia (2002) 45: 309. doi:10.1007/s00125-001-0728-y

Abstract.

The mammalian insulin gene is exclusively expressed in the beta cells of the endocrine pancreas. Two decades of intensive physiological and biochemical studies have led to the identification of regulatory sequence motifs along the insulin promoter and to the isolation of transcription factors which interact to activate gene transcription. The majority of the islet-restricted (BETA2, PDX-1, RIP3b1-Act/C1) and ubiquitous (E2A, HEB) insulin-binding proteins have been characterized. Transcriptional regulation results not only from specific combinations of these activators through DNA-protein and protein-protein interactions, but also from their relative nuclear concentrations, generating a cooperativity and transcriptional synergism unique to the insulin gene. Their DNA binding activity and their transactivating potency can be modified in response to nutrients (glucose, NEFA) or hormonal stimuli (insulin, leptin, glucagon like peptide-1, growth hormone, prolactin) through kinase-dependent signalling pathways (PI3-K, p38MAPK, PKA, CaMK) modulating their affinities for DNA and/or for each other. From the overview of the research presented, it is clear that much more study is required to fully comprehend the mechanisms involved in the regulated-expression of the insulin gene in the beta cell to prevent its impairment in diabetes. [Diabetologia (2002) 45: 309–326]

Keywords Insulin genebeta celltranscription factorpromoterPDX-1glucosediabetesNEFAleptinGLP-1.
Download to read the full article text

Copyright information

© Springer-Verlag Berlin Heidelberg 2002