Glucose regulation of insulin gene expression in pancreatic β-cells
| Autor: | Sreenath S. Andrali, Nathan L. Vanderford, Sabire Özcan, Megan L. Sampley |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Maf Transcription Factors Large medicine.medical_treatment Nerve Tissue Proteins Biology Biochemistry Histone Deacetylases Transactivation Insulin-Secreting Cells Maf Transcription Factors Internal medicine Basic Helix-Loop-Helix Transcription Factors medicine Animals Humans Insulin Molecular Biology Transcription factor Homeodomain Proteins Regulation of gene expression Cell Biology Protein Transport Insulin receptor Endocrinology Gene Expression Regulation NEUROD1 Trans-Activators biology.protein Blood sugar regulation |
| Zdroj: | Biochemical Journal. 415:1-10 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20081029 |
| Popis: | Production and secretion of insulin from the beta-cells of the pancreas is very crucial in maintaining normoglycaemia. This is achieved by tight regulation of insulin synthesis and exocytosis from the beta-cells in response to changes in blood glucose levels. The synthesis of insulin is regulated by blood glucose levels at the transcriptional and post-transcriptional levels. Although many transcription factors have been implicated in the regulation of insulin gene transcription, three beta-cell-specific transcriptional regulators, Pdx-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation 1) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A), have been demonstrated to play a crucial role in glucose induction of insulin gene transcription and pancreatic beta-cell function. These three transcription factors activate insulin gene expression in a co-ordinated and synergistic manner in response to increasing glucose levels. It has been shown that changes in glucose concentrations modulate the function of these beta-cell transcription factors at multiple levels. These include changes in expression levels, subcellular localization, DNA-binding activity, transactivation capability and interaction with other proteins. Furthermore, all three transcription factors are able to induce insulin gene expression when expressed in non-beta-cells, including liver and intestinal cells. The present review summarizes the recent findings on how glucose modulates the function of the beta-cell transcription factors Pdx-1, NeuroD1 and MafA, and thereby tightly regulates insulin synthesis in accordance with blood glucose levels. |
| Databáze: | OpenAIRE |
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