Transcription factors in islet development and physiology - Role of PDX-1 in beta-cell function

被引:78
|
作者
Melloul, D [1 ]
机构
[1] Hebrew Univ Jerusalem, Ctr Med, Dept Endocrinol & Metab, IL-91120 Jerusalem, Israel
来源
GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOR DISEASE: MOLECULAR AND CELL BIOLOGICAL ASPECTS | 2004年 / 1014卷
关键词
pancreas; islet; beta cell; insulin; transcription factors; PDX-1; diabetes;
D O I
10.1196/annals.1294.003
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
Differentiation of early foregut endoderm into pancreatic endocrine and exocrine cells depends on a cascade of gene activation events controlled by various transcription factors. The first molecular marker identified that specifies the early pancreatic epithelium is the homeodomain-containing transcription factor PDX-1. Its absence in mice and humans during development leads to agenesis of the pancreas. Later, it becomes restricted primarily to beta-cells where it regulates the expression of beta-cell-specific genes, and, most importantly, mediates the glucose effect on insulin gene transcription. Although exposure of beta-cells to high glucose concentrations for relatively short periods stimulates insulin gene expression, chronic exposure has adverse effects on many beta-cell functions, including insulin gene transcription. These events appear to correlate with pdx-1 gene expression and its ability to bind the insulin gene. We consider that loss of PDX-1 function or altered pdx-1 gene expression due to mutations or functional impairment of transcription factors controlling its expression can lead to diabetes.
引用
收藏
页码:28 / 37
页数:10
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