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.
Review Article| September 12 2008
Glucose regulation of insulin gene expression in pancreatic β-cells
Sreenath S. Andrali;
Megan L. Sampley;
Nathan L. Vanderford;
Sabire Özcan 2
1Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 South Limestone, Lexington, KY 40536, U.S.A.
2To whom correspondence should be addressed (email firstname.lastname@example.org).
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Sreenath S. Andrali, Megan L. Sampley, Nathan L. Vanderford, Sabire Özcan; Glucose regulation of insulin gene expression in pancreatic β-cells. Biochem J 1 October 2008; 415 (1): 1–10. doi: https://doi.org/10.1042/BJ20081029
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