Extracellular ATP-derived nucleotides and nucleosides are important autocrine regulators of adipocyte function. However, the mechanisms of ATP release from adipocytes are not known.
Samantha E. Adamson et al. now identified Panx1 channels as mediators of controlled extracellular nucleotide release from adipocytes. Further, they demonstrated that Panx1-dependent ATP release is required for full activation of insulin-induced glucose uptake in adipocytes and identified insulin as a novel mediator of Panx1 channel activation.
The cover illustration summarizes the proposed signaling pathway in which insulin stimulates glucose uptake by activation of Panx1: Insulin mediates opening of Panx1 channels and triggers ATP release from adipocytes. ATP signals through the purinergic P2 receptor family or is converted to adenosine (ADO) by the action of ectonucleotidases. After receptor binding, ADO stimulates glucose uptake by promoting the incorporation of Glut4 into the plasma membrane.