Insulin inhibition of glucocorticoid-stimulated gene transcription: requirement for an insulin response element?

The glucocorticoid hormone receptor binds to regulatory elements of target genes and activates transcription through interactions with coactivators. For a subset of genes, glucocorticoid receptor activity is inhibited by insulin. The present paper analyzes recent data on the molecular mechanisms whereby insulin exerts this antiglucocorticoid effect. Two models are proposed. In the first model insulin controls the activity of an insulin-responsive factor bound to an insulin-responsive DNA element. In a second model, insulin targets a non-DNA bound coactivator of the glucocorticoid receptor. Here, the gene-specificity of the effect of insulin is conferred by the combined action of the glucocorticoid receptor, of DNA-bound transcription factors and of coactivators, which form a higher order structure that binds to a DNA sequence called glucocorticoid/insulin responsive unit