Modulating glucocorticoid receptor translocation in the liver – therapeutic relevance for HDAC6?

In vitro the histone deacetylase 6 (HDAC6) has been shown to be a major deacetylase of heat shock protein 90 (HSP90). It is mediating glucocorticoid receptor (GR) ligand interaction since the correct folding of the GR as HSP90 client protein depends on HSP90 acetylation status. We could recently show that HDAC6 deficiency results in an attenuation of dex-induced whole-body glucose intolerance as well as insulin resistance. In the present study we investigated the underlying mechanism of HDAC6 as a modulator of metabolic GR function. For this study we worked with primary hepatocytes isolated from wildtype (wt) an…