Nedd4 family interacting protein 1 (Ndfip1) promotes death of pancreatic beta cells
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Updated: Apr 4, 2026
Isolated Pancreatic Islet Treatment and Apoptosis Measurement
Published on: May 2, 2025
Avital Beck1, Hadas Shatz-Azoulay1, Yaron Vinik1
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract:
High-throughput siRNA screening was employed to identify novel genes that regulate cytokine-induced death of pancreatic β-cells. One of the 'hits' was Nedd4 family interacting protein 1 (Ndfip1), an adaptor and activator of Nedd4-family ubiquitin ligases. Silencing of Ndfip1 inhibited cytokine-induced apoptosis of mouse and human pancreatic islets and promoted glucose-stimulated insulin secretion. These effects were associated with an increase in the cellular content of JunB, a potent inhibitor of ER stress and apoptosis. Silencing of Ndfip1 also increased the expression of ATF4, IRE-1α, and the spliced form of XBP that govern the unfolded protein response (UPR) and relieve cytokine-induced ER stress, while overexpression of Ndfip1 exerted opposite effects. These findings implicate Ndfip1 in the degradation of JunB; inhibition of the UPR and insulin secretion; and promotion of cytokine-induced death of pancreatic β-cells.
Insights
Nedd4 family interacting protein 1 (Ndfip1) regulates pancreatic beta-cell death and insulin secretion. Inhibiting Ndfip1 protects beta-cells from cytokine-induced apoptosis and enhances insulin release by modulating JunB and the unfolded protein response.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Cytokine-induced apoptosis threatens pancreatic beta-cell function.
- Identifying regulators of beta-cell death is crucial for diabetes research.
Purpose of the Study:
- To identify novel genes regulating cytokine-induced pancreatic beta-cell death.
- To elucidate the role of Nedd4 family interacting protein 1 (Ndfip1) in beta-cell function.
Main Methods:
- High-throughput siRNA screening in pancreatic beta-cells.
- Analysis of apoptosis, insulin secretion, JunB, and unfolded protein response (UPR) markers.
- Utilized mouse and human pancreatic islets.
Main Results:
- Ndfip1 silencing inhibited cytokine-induced apoptosis in mouse and human islets.
- Ndfip1 inhibition promoted glucose-stimulated insulin secretion.
- Ndfip1 regulates JunB levels and modulates UPR components (ATF4, IRE-1α, XBP1s).
Conclusions:
- Ndfip1 promotes pancreatic beta-cell death and inhibits insulin secretion.
- Ndfip1 appears to mediate JunB degradation and suppress the UPR.
- Targeting Ndfip1 may offer therapeutic potential for beta-cell protection.
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