Nephrin, a transmembrane protein, is involved in pancreatic beta-cell survival signaling

Katerina Kapodistria, Effie Photini Tsilibary, Panagiotis Politis, Petros Moustardas, Aristidis Charonis, Paraskevi Kitsiou

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Nephrin, a cell surface signaling receptor, regulates podocyte function in health and disease. We study the role of nephrin in β-cell survival signaling. We report that in mouse islet β-cells and the mouse pancreatic beta-cell line (βTC-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 PKCα 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 β-cell survival and suggest that glucose-induced changes in nephrin signaling may contribute to gradual pancreatic β-cell loss in type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)112-128
Number of pages17
JournalMolecular and Cellular Endocrinology
StatePublished - Jan 5 2015

Bibliographical note

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© 2014 The Authors.


  • Diabetic mouse pancreatic islets
  • High glucose
  • Nephrin internalization
  • Nephrin signaling
  • PI3K-Akt survival signaling
  • Pancreatic β-cells


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