Regulation of gene expression by glucose

Abstract

In addition to its metabolic function, glucose modulates gene expression which is crucial in adapting cells to variations in glycaemia. We summarize recent advances in our understanding of regulation of gene expression by glucose. In-vivo and in-vitro experiments demonstrated that glucose regulates the transcription of genes encoding not only lipogenic and glycolytic enzymes but also proteins involved in global cell functions. The molecular mechanisms have begun to be elucidated, and the transcription factor carbohydrate responsive element-binding protein has emerged as a key actor, at least in liver. More recently, other candidates have been proposed, such as liver X receptors. In pathological situations, altered glycaemic control, as observed in diabetes mellitus, is associated with increased risk for microvascular and macrovascular complications. Recent findings suggest that changes in gene expression occurring in response to hyperglycaemia represent a novel component of glucotoxicity. Until recently, the direct transcriptional effects of glucose were underestimated, and insulin was considered to be the major regulator of gene expression in response to glycaemic variation. The recent discovery and characterization of transcription factors mediating the glucose response demonstrate that glucose, like fatty acids and other key nutrients, can directly control gene expression.