A mechanism for activating AMPK, a metabolic sensor important for maintaining cellular energy balance which is a validated target for the treatment of diabetes, is reported this week in Nature Chemical Biology. As the work helps us to further understand the underlying regulation of AMPK activity, it may provide a new therapeutic opportunity for treating diabetes.
Qiao Wu, Tianwei Lin and colleagues identify a new pathway involving the orphan nuclear receptor Nur77 that negatively regulates AMPK by sequestering LKB1, an activator of AMPK, away from its target. The pathway was revealed by mechanistic studies of a newly discovered compound that blocks Nur77-LKB1 interaction, releasing LKB1 to activate AMPK. In multiple mouse models of diabetes, their compound improved blood glucose levels, insulin levels and response to glucose challenge.
More work will be needed to determine whether the compound can be adapted for clinical use, but the discovery of this pathway creates new opportunities for scientists to activate AMPK for the treatment of diabetes.