Glucose regulation of insulin gene expression in pancreatic β-cells

作者：Sreenath S. Andrali, Megan L. Sampley, Nathan L. Vanderford, Sabire Özcan · 发表于：Biochemical Journal · 年份：2008 · DOI：10.1042/bj20081029 · 被引用次数：202 · 研究领域：Pancreatic function and diabetes、Metabolism, Diabetes, and Cancer、Diabetes and associated disorders

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 modula...