In addition, we report the first evidence that activation of human adipocyte P2Y2R by ATP/UTP contributes to insulin resistance in mature adipocytes, in which a specific insulin receptors downstream signaling pathway, including PIP3 production, AKT phosphorylation, GLUT4 translocation, and glucose uptake is impaired by P2Y2R activation. Here, AKT1 is linked to Insulin resistance.