Yang Jichun, Wang Chunjiong, Li Jing, Burkhardt Brant R, Robert-Cooperman Claudia E, Wilson Camella, Gao Zhiyong, Wolf Bryan A
Department of Physiology and Pathophysiology, Peking University School of Basical Medicine, Beijing 100191, PR China.
FEBS Lett. 2009 Sep 17;583(18):3009-15. doi: 10.1016/j.febslet.2009.08.008. Epub 2009 Aug 14.
PANDER is a cytokine co-secreted with insulin from islet beta-cells. To date, the physiological function of PANDER remains largely unknown. Here we show that PANDER binds to the liver membrane by (125)I-PANDER saturation and competitive binding assays. In HepG2 cells, pre-treatment with PANDER ranging from 4 pM to 4 nM for 8h resulted in a maximal inhibition of insulin-stimulated activation of insulin receptor and insulin receptor substrate 1 by 52% and 63%, respectively. Moreover, PANDER treatment also reduced insulin-stimulated PI3K and pAkt levels by 55% and 48%, respectively. In summary, we have identified the liver as a novel target for PANDER, and PANDER may be involved in the progression of diabetes by regulating hepatic insulin signaling pathways.
PANDER是一种与胰岛素共同从胰岛β细胞分泌的细胞因子。迄今为止，PANDER的生理功能在很大程度上仍不清楚。在此我们通过（125）I-PANDER饱和及竞争性结合试验表明，PANDER可与肝细胞膜结合。在HepG2细胞中，用4 pM至4 nM的PANDER预处理8小时，导致胰岛素刺激的胰岛素受体及胰岛素受体底物1的激活分别受到最大52%和63%的抑制。此外，PANDER处理还分别使胰岛素刺激的PI3K和pAkt水平降低了55%和48%。总之，我们已确定肝脏是PANDER的一个新靶点，且PANDER可能通过调节肝脏胰岛素信号通路参与糖尿病的进展。
