PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells.
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.
Yang
Jichun
J
Department of Physiology and Pathophysiology, Peking University School of Basical Medicine, Beijing 100191, PR China. yangj@bjmu.edu.cn
Wang
Chunjiong
C
Li
Jing
J
Burkhardt
Brant R
BR
Robert-Cooperman
Claudia E
CE
Wilson
Camella
C
Gao
Zhiyong
Z
Wolf
Bryan A
BA
D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects*
D016207:Cytokines; D007328:Insulin; C504749:PANDER protein, mouse; D011994:Recombinant Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt