| First Author | Cunha DA | Year | 2016 |
| Journal | Cell Death Differ | Volume | 23 |
| Issue | 12 | Pages | 1995-2006 |
| PubMed ID | 27588705 | Mgi Jnum | J:259862 |
| Mgi Id | MGI:6141773 | Doi | 10.1038/cdd.2016.89 |
| Citation | Cunha DA, et al. (2016) Thrombospondin 1 protects pancreatic beta-cells from lipotoxicity via the PERK-NRF2 pathway. Cell Death Differ 23(12):1995-2006 |
| abstractText | The failure of beta-cells has a central role in the pathogenesis of type 2 diabetes, and the identification of novel approaches to improve functional beta-cell mass is essential to prevent/revert the disease. Here we show a critical novel role for thrombospondin 1 (THBS1) in beta-cell survival during lipotoxic stress in rat, mouse and human models. THBS1 acts from within the endoplasmic reticulum to activate PERK and NRF2 and induce a protective antioxidant defense response against palmitate. Prolonged palmitate exposure causes THBS1 degradation, oxidative stress, activation of JNK and upregulation of PUMA, culminating in beta-cell death. These findings shed light on the mechanisms leading to beta-cell failure during metabolic stress and point to THBS1 as an interesting therapeutic target to prevent oxidative stress in type 2 diabetes. |
