Glucose regulation of insulin gene expression in pancreatic β-cells

被引:149
作者
Andrali, Sreenath S. [1 ]
Sampley, Megan L. [1 ]
Vanderford, Nathan L. [1 ]
Ozcan, Sabire [1 ]
机构
[1] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA
关键词
diabetes; glucose; insulin; NeuroD1 (neurogenic differentiation 1); pancreatic and duodenal homeobox-1 (Pdx-1); V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; (MafA);
D O I
10.1042/BJ20081029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Production and secretion of insulin from the P-cells of the pancreas is very crucial in maintaining normoglycaemia. This is achieved by tight regulation of insulin synthesis and exocytosis from the P-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 P-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 P-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 P-cell transcription factors at multiple levels. These include changes in expression levels, subcellular localization, DNA-binding activity, transactivation capability and interaction with other proteins. Furthennore, 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 P-cell transcription factors Pdx-1, NeuroD1 and MafA, and thereby tightly regulates insulin synthesis in accordance with blood glucose levels.
引用
收藏
页码:1 / 10
页数:10
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