Regulation of gene expression by insulin

Abstract

While insulin has long been known to modulate intracellular metabolism by altering the activity or intracellular location of various enzymes, it is only in the past 10 years that the regulation of gene expression by insulin has been recognized as a major action of this hormone. This review principally focuses on the regulation of gene transcription by insulin, although recent progress in the understanding of insulin-regulated mRNA stability and translation is also summarized. The identification of cis-acting elements and associated trans-acting factors through which insulin either increases or decreases the transcription of specific genes is reviewed in detail. Recent advances in the understanding of the mechanisms of insulin signaling are discussed in the context of insulin-regulated gene transcription, and emphasis is placed on the gaps that remain between the upstream signaling molecules and the downstream trans-acting factors whose binding/transactivation potential is ultimately regulated. Finally, potential gene expression defects that may contribute to the pathophysiology of non-insulin-dependent diabetes mellitus and hypertriglyceridemia are considered.