Regulation of insulin gene transcription

Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem, Israel.
Diabetologia (Impact Factor: 6.67). 04/2002; 45(3):309-26. DOI: 10.1007/s00125-001-0728-y
Source: PubMed


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.

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Available from: Danielle Melloul, Jul 27, 2015
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    • "expression of the VGF precursor protein (Fig. 3A, inset), an effect blocked by pretreatment with cyclohexamide. This suggested that the effect was transcriptionally dependent, but we also cannot exclude the glucose-mediated translational regulation of mRNAs, which has been previously reported (Melloul et al. 2002). In a similar fashion, TLQP- 62 increased Ins1 and Vgf gene expression but not that of Ins2 at 2 h (Fig. 3B). "
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