The insulin promoter region has many
Enzastaurin for transcription factors and confers both tissue-specific expression and metabolic regulation of the insulin gene. The most critical cis-acting DNA elements involved in transcriptional activation in vitro are referred to as the A and E elements, pancreatic/duodenal homeobox-1(PDX-1) and BETA2 binding sites, respectively. PDX-1 is a homeodomain protein that binds to the A3 box of the insulin gene [9] and interacts with proteins of the basic helix–loop–helix (bHLH) family that bind to the E1 box [10]. BETA2 heterodimerizes with ubiquitous bHLH proteins of the E2A family to regulate transcription of the insulin gene and other β-cell specific genes. Therefore, the decreased insulin gene
expression caused by AMPK activation might be induced by the inhibition of PDX-1 and BETA2 gene expression, or by inhibiting the binding of those factors with the insulin promoter. However, the mechanism by which AMPK regulates insulin gene expression is not well defined.
