PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells
| Autor: | Zhiyong Gao, Jichun Yang, Jing Li, Claudia E. Robert-Cooperman, Chunjiong Wang, Brant R. Burkhardt, Camella G. Wilson, Bryan A. Wolf |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Liver cytology medicine.medical_treatment Biophysics Binding Competitive Biochemistry PANDER Mice Phosphatidylinositol 3-Kinases Insulin resistance Structural Biology Cell Line Tumor Insulin receptor substrate Internal medicine Genetics medicine Animals Humans Insulin Cytokine Molecular Biology PI3K/AKT/mTOR pathway Dose-Response Relationship Drug biology Insulin signaling pathway Cell Membrane Cell Biology medicine.disease Recombinant Proteins IRS1 Insulin receptor Endocrinology Liver biology.protein Cytokines Signal transduction Proto-Oncogene Proteins c-akt Protein Binding Signal Transduction |
| Zdroj: | FEBS Letters. 583:3009-3015 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/j.febslet.2009.08.008 |
| Popis: | PANDER is a cytokine co-secreted with insulin from islet β-cells. To date, the physiological function of PANDER remains largely unknown. Here we show that PANDER binds to the liver membrane by 125I-PANDER saturation and competitive binding assays. In HepG2 cells, pre-treatment with PANDER ranging from 4pM to 4nM 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. |
| Databáze: | OpenAIRE |
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