par Andrade Da Cunha, Daniel 
;Cito, Monia ;Carlsson, Per Ola;Vanderwinden, Jean-Marie ;Molkentin, Jeffery;Bugliani, Marco;Marchetti, Piero;Eizirik, Decio L. ;Cnop, Miriam
Référence Cell death and differentiation, 23, 12, page (1995-2006)
Publication Publié, 2016-12
;Cito, Monia ;Carlsson, Per Ola;Vanderwinden, Jean-Marie ;Molkentin, Jeffery;Bugliani, Marco;Marchetti, Piero;Eizirik, Decio L. ;Cnop, Miriam Référence Cell death and differentiation, 23, 12, page (1995-2006)
Publication Publié, 2016-12
Article révisé par les pairs
| Résumé : | The failure of β-cells has a central role in the pathogenesis of type 2 diabetes, and the identification of novel approaches to improve functional β-cell mass is essential to prevent/revert the disease. Here we show a critical novel role for thrombospondin 1 (THBS1) in β-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 β-cell death. These findings shed light on the mechanisms leading to β-cell failure during metabolic stress and point to THBS1 as an interesting therapeutic target to prevent oxidative stress in type 2 diabetes. |
