Transcriptional Regulation of the Insulin Receptor Gene Promoter

The human insulin receptor is a membrane bound glycoprotein which is found on the surface of most cells. Like many growth factor receptors, the insulin receptor is a tyrosine kinase. The receptor is a heterotetramer composed of 2 alpha-and 2 beta-subunits. The alpha-subunit is located extracellularly where it binds insulin while the beta-subunit spans the membrane and contains the tyrosine kinase domain. The presence of this receptor is probably necessary for normal cell growth. Specialized cells such as myocytes and adipocytes have evolved mechanisms to elevate levels of this protein on their surface which allows these cells to be especially sensitive to the effects of insulin. In addition, the number of insulin receptor has been shown to be regulated by systemic factors such as hormones1 and nutrients such as glucose.2 Many investigators have cloned and analyzed the human insulin receptor promoter in an attempt to identify individual elements which are responsible for these effects. In this review, I will summarize the progress in this field and will discuss some of the conflicting data which has resulted.