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Thrombospondin 1 pr...
Thrombospondin 1 protects pancreatic beta-cells from lipotoxicity via the PERK-NRF2 pathway
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- Cunha, Daniel A. (författare)
- Univ Libre Bruxelles, ULB Ctr Diabet Res, CP-618,Route Lennik 808, B-1070 Brussels, Belgium.
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- Cito, Monia (författare)
- Univ Libre Bruxelles, ULB Ctr Diabet Res, CP-618,Route Lennik 808, B-1070 Brussels, Belgium.
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- Carlsson, Per-Ola (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Vanderwinden, Jean-Marie (författare)
- Univ Libre Bruxelles, Light Microscopy Facil, B-1070 Brussels, Belgium.
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- Molkentin, Jeffery D. (författare)
- Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
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- Bugliani, Marco (författare)
- Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy.
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- Marchetti, Piero (författare)
- Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy.
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- Eizirik, Decio L. (författare)
- Univ Libre Bruxelles, ULB Ctr Diabet Res, CP-618,Route Lennik 808, B-1070 Brussels, Belgium.
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- Cnop, Miriam (författare)
- Univ Libre Bruxelles, ULB Ctr Diabet Res, CP-618,Route Lennik 808, B-1070 Brussels, Belgium.;Univ Libre Bruxelles, Erasmus Hosp, Div Endocrinol, B-1070 Brussels, Belgium.
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Univ Libre Bruxelles, ULB Ctr Diabet Res, CP-618,Route Lennik 808, B-1070 Brussels, Belgium Institutionen för medicinsk cellbiologi (creator_code:org_t)
- 2016-09-02
- 2016
- Engelska.
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Ingår i: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 23:12, s. 1995-2006
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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