Thrombospondin 1 protects pancreatic ?-cells from lipotoxicity via the PERK-NRF2 pathway.
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ABSTRACT:
SUBMITTER: Cunha DA
PROVIDER: S-EPMC5136495 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
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Thrombospondin 1 protects pancreatic β-cells from lipotoxicity via the PERK-NRF2 pathway.
Cunha Daniel A DA Cito Monia M Carlsson Per-Ola PO Vanderwinden Jean-Marie JM Molkentin Jeffery D JD Bugliani Marco M Marchetti Piero P Eizirik Décio L DL Cnop Miriam M
Cell death and differentiation 20160902 12
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 p ...[more]
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