Glucose regulation of insulin gene expression in pancreatic β-cells
- 12 September 2008
- journal article
- review article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 415 (1), 1-10
- https://doi.org/10.1042/bj20081029
Abstract
Production and secretion of insulin from the β-cells of the pancreas is very crucial in maintaining normoglycaemia. This is achieved by tight regulation of insulin synthesis and exocytosis from the β-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 β-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 β-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 β-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-β-cells, including liver and intestinal cells. The present review summarizes the recent findings on how glucose modulates the function of the β-cell transcription factors Pdx-1, NeuroD1 and MafA, and thereby tightly regulates insulin synthesis in accordance with blood glucose levels.Keywords
This publication has 164 references indexed in Scilit:
- O-GlcNAc Regulates FoxO Activation in Response to GlucoseOnline Journal of Public Health Informatics, 2008
- Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic β-cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- Glucose Mediates the Translocation of NeuroD1 by O-Linked GlycosylationOnline Journal of Public Health Informatics, 2007
- MafB is required for islet β cell maturationProceedings of the National Academy of Sciences of the United States of America, 2007
- Glucose Induces MafA Expression in Pancreatic Beta Cell Lines via the Hexosamine Biosynthetic PathwayOnline Journal of Public Health Informatics, 2007
- MAFA controls genes implicated in insulin biosynthesis and secretionDiabetologia, 2006
- MafA differentiates rat intestinal cells into insulin-producing cellsBiochemical and Biophysical Research Communications, 2006
- A switch from MafB to MafA expression accompanies differentiation to pancreatic β-cellsDevelopmental Biology, 2006
- Roles of maf family proteins in lens developmentDevelopmental Dynamics, 2004
- Insulin-promoter-factor 1 is required for pancreas development in miceNature, 1994