Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues

Thiazolidinediones (TZDs) are insulin-sensitizing agents used in the treatment of type 2 diabetes. A widely held view is that their action is secondary to transcriptional events that occur when TZDs bind to the nuclear receptor PPARγ in the adipocyte and stimulate adipogenesis. It has been proposed that this increases insulin sensitivity, at least in part, by increasing the expression and release of adiponectin, an adipokine that activates the fuel-sensing enzyme AMP-activated protein kinase (AMPK). In this study, we report that TZDs also acutely activate AMPK in skeletal muscle and other tissues by a mechanism that is likely independent of PPARγ-regulated gene transcription. Thus incubation of isolated rat EDL muscles in medium containing 5 μM troglitazone for 15 min (too brief to be attributable to transcription) significantly increased pAMPK and pACC. At a concentration of 100 μM, troglitazone maximally increased these parameters and caused twofold increases in 2-deoxy-d-glucose uptake and the oxidatio...