Insulin action, insulin resistance, and their link to histone acetylation

Abstract

Posttranslational covalent histone modifications, usually referred as epigenetic changes, including acetylation, methylation and phosphorylation; and DNA methylation on cytosines are main mechanism of regulation of chromatin structure and transcription. Insulin, the main anabolic hormone, exerts pleiotropic actions by acting on insulin-sensitive tissues. In addition to the control of metabolism, insulin extensively modulates gene expression. The relevance of insulin-dependent gene regulation has been confirmed by the observation that in insulin resistance and T2DM, insulin-regulated gene expression is impaired. In this chapter, we provide an overview of the current knowledge on the link between the hormonal action of insulin, via its intracellular signaling pathways, and the influence of these pathways on epigenetic modifications that act as central regulators of insulin-dependent gene transcription. We specifically focus on the link between insulin signaling and transcriptional control via histone acetylation. The occurrence of alterations of proper acetylation patterns within the context of insulin resistance and type 2 diabetes mellitus (T2DM) will also be discussed. Reversing these alterations might provide novel therapeutic options against insulin resistance and/or T2DM.