Abstract
Aims: Previous studies have reported the induction of the viperin in isolated human islets exposed to proinflammatory cytokines and coxsackieviruses, as well as in the serum of people at risk of type 1 diabetes. We hypothesised that viperin plays a role in beta cell apoptosis during the development of type 1 diabetes. This project aimed to investigate the role of viperin in cytokine-mediated beta cell apoptosis.
Methods: siRNA knockdown of viperin was performed in INS1 cells followed by an assessment of gene expression and beta cell apoptosis. Apoptosis was also studied in islets isolated from viperin knockout (Rsad2KO) and control mice.
Results: In INS1 cells and isolated wild-type mouse islets, viperin mRNA expression was highly induced within a few hours of exposure to proinflammatory cytokines, and expression levels decreased over time. Interestingly, apoptosis starts to peak as viperin levels decreased. siRNA knockdown of viperin in INS1 cells resulted in increased cytokine-induced apoptosis compared to siRNA controls (3.5-fold increase with cytokines in siViperin cells; 1.5-fold increase with cytokines in siControl cells; p < 0.0001 by t-test; n = 13). Similarly, cytokine-induced apoptosis was increased in isolated islets of Rsad2KO mice compared to wild-type controls (3.5-fold increase with cytokine treatment of Rsad2KO islets; 2.5-fold increase with cytokine treatment of wild-type islets; p < 0.05 by t-test; n = 12). RT-qPCR revealed that viperin influenced the expression of cytokine-response genes including NF-kb, JAK2 and STAT1, and the ER stress marker CHOP (DDIT3).
Conclusion: Our data indicate that viperin expression plays a protective role against cytokine-mediated beta cell apoptosis.
Methods: siRNA knockdown of viperin was performed in INS1 cells followed by an assessment of gene expression and beta cell apoptosis. Apoptosis was also studied in islets isolated from viperin knockout (Rsad2KO) and control mice.
Results: In INS1 cells and isolated wild-type mouse islets, viperin mRNA expression was highly induced within a few hours of exposure to proinflammatory cytokines, and expression levels decreased over time. Interestingly, apoptosis starts to peak as viperin levels decreased. siRNA knockdown of viperin in INS1 cells resulted in increased cytokine-induced apoptosis compared to siRNA controls (3.5-fold increase with cytokines in siViperin cells; 1.5-fold increase with cytokines in siControl cells; p < 0.0001 by t-test; n = 13). Similarly, cytokine-induced apoptosis was increased in isolated islets of Rsad2KO mice compared to wild-type controls (3.5-fold increase with cytokine treatment of Rsad2KO islets; 2.5-fold increase with cytokine treatment of wild-type islets; p < 0.05 by t-test; n = 12). RT-qPCR revealed that viperin influenced the expression of cytokine-response genes including NF-kb, JAK2 and STAT1, and the ER stress marker CHOP (DDIT3).
Conclusion: Our data indicate that viperin expression plays a protective role against cytokine-mediated beta cell apoptosis.
| Original language | English |
|---|---|
| Article number | A29 (P69) |
| Pages (from-to) | 14 |
| Number of pages | 1 |
| Journal | Diabetic Medicine |
| Volume | 38 |
| Issue number | S1 |
| Early online date | 18 Apr 2021 |
| DOIs | |
| Publication status | Published - Apr 2021 |
| Event | Diabetes UK Professional Conference 2021 - Online Duration: 19 Apr 2021 → 30 Apr 2021 |
