Histone deacetylase 6– HDAC6– a new regulator of glucocorticoid receptor-mediated metabolic processes

The glucocorticoid receptor (GR) is an important regulator of insulin sensitivity and glucose tolerance. Since the histone deacetylase 6 (HDAC6) deacetylates heat shock protein 90, a GR chaperone, we investigated the effect of HDAC6 on GR function in a metabolic context in vivo and in vitro. Wildtype (wt) and hdac6-deficient (HDAC6ko) mice were subjected to 3 week 1mg/kg intraperitoneal (ip) dexamethasone (dex) treatment. In wt-mice dex injection resulted in a marked glucose intolerance (ipGTT: glucose 30min: vehicle 210±9.9.mg/dl vs. dex: 273±30.6mg/dl, p