| First Author | Kapodistria K | Year | 2015 |
| Journal | Mol Cell Endocrinol | Volume | 400 |
| Pages | 112-28 | PubMed ID | 25448064 |
| Mgi Jnum | J:220285 | Mgi Id | MGI:5634069 |
| Doi | 10.1016/j.mce.2014.11.003 | Citation | Kapodistria K, et al. (2015) Nephrin, a transmembrane protein, is involved in pancreatic beta-cell survival signaling. Mol Cell Endocrinol 400:112-28 |
| abstractText | Nephrin, a cell surface signaling receptor, regulates podocyte function in health and disease. We study the role of nephrin in beta-cell survival signaling. We report that in mouse islet beta-cells and the mouse pancreatic beta-cell line (betaTC-6 cells) nephrin is associated and partly co-localized with PI3-kinase. Incubation of cells with functional anti-nephrin antibodies induced nephrin clustering at the plasma membrane, nephrin phosphorylation and recruitment of PI3-kinase to nephrin thus resulting in increased PI3K-dependent Akt phosphorylation and augmented phosphorylation/inhibition of pro-apoptotic Bad and FoxO. Nephrin silencing abolished Akt activation and increased susceptibility of cells to apoptosis. High glucose impaired nephrin signaling, increased nephrin internalization and up-regulated PKCalpha expression. Interestingly, a marked decrease in nephrin expression and phosphorylated Akt was observed in pancreatic islets of db/db lepr-/- diabetic mice. Our findings revealed that nephrin is involved in beta-cell survival and suggest that glucose-induced changes in nephrin signaling may contribute to gradual pancreatic beta-cell loss in type 2 diabetes. |
