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http://hdl.handle.net/2445/164869
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DC Field | Value | Language |
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dc.contributor.author | Botteri, Gaia | - |
dc.contributor.author | Salvadó Serra, Laia | - |
dc.contributor.author | Gumà i Garcia, Anna Maria | - |
dc.contributor.author | Lee Hamilton, D. | - |
dc.contributor.author | Meakin, Paul J. | - |
dc.contributor.author | Montagut, Gemma | - |
dc.contributor.author | Ashford, Michael | - |
dc.contributor.author | Ceperuelo-Mallafré, Victoria | - |
dc.contributor.author | Fernández-Veledo, Sonia | - |
dc.contributor.author | Vendrell, Joan | - |
dc.contributor.author | Calderón Domínguez, María | - |
dc.contributor.author | Serra i Cucurull, Dolors | - |
dc.contributor.author | Herrero Rodríguez, Laura | - |
dc.contributor.author | Pizarro Delgado, Javier | - |
dc.contributor.author | Barroso Fernández, Emma | - |
dc.contributor.author | Palomer Tarridas, Francesc Xavier | - |
dc.contributor.author | Vázquez Carrera, Manuel | - |
dc.date.accessioned | 2020-06-09T09:41:38Z | - |
dc.date.available | 2020-06-09T09:41:38Z | - |
dc.date.issued | 2018-03-09 | - |
dc.identifier.issn | 0026-0495 | - |
dc.identifier.uri | http://hdl.handle.net/2445/164869 | - |
dc.description.abstract | Objective -secretase/-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a key enzyme involved in Alzheimer's disease that has recently been implicated in insulin-independent glucose uptake in myotubes. However, it is presently unknown whether BACE1 and the product of its activity, soluble APPsAPPcontribute to lipid-induced inflammation and insulin resistance in skeletal muscle cells. Materials/Methods Studies were conducted in mouse C2C12 myotubes, skeletal muscle from Bace1-/-mice and mice treated with sAPP and adipose tissue and plasma from obese and type 2 diabetic patients. Results We show that BACE1 inhibition or knockdown attenuates palmitate-induced endoplasmic reticulum (ER) stress, inflammation, and insulin resistance and prevents the reduction in Peroxisome Proliferator- Activated Receptor Co-activator 1 (PGC-1) and fatty acid oxidation caused by palmitate in myotubes. The effects of palmitate on ER stress, inflammation, insulin resistance, PGC-1 down-regulation, and fatty acid oxidation were mimicked by soluble APP in vitro. BACE1 expression was increased in subcutaneous adipose tissue of obese and type 2 diabetic patients and this was accompanied by a decrease in PGC-1 mRNA levels and by an increase in sAPPplasma levels of obese type 2 diabetic patients compared to obese non-diabetic subjects. Acute sAPP administration to mice reduced PGC-1 levels and increased inflammation in skeletal muscle and decreased insulin sensitivity. Conclusions Collectively, these findings indicate that the BACE1 product sAPP is a key determinant in ER stress, inflammation and insulin resistance in skeletal muscle and gluconeogenesis in liver. | - |
dc.format.extent | 17 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | W.B. Saunders | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1016/j.metabol.2018.03.005 | - |
dc.relation.ispartof | Metabolism-Clinical and Experimental, 2018, vol. 85, p. 59-75 | - |
dc.relation.uri | https://doi.org/10.1016/j.metabol.2018.03.005 | - |
dc.rights | cc-by-nc-nd (c) W.B. Saunders, 2018 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Insulina | - |
dc.subject.classification | Farmacologia | - |
dc.subject.classification | Farmacocinètica | - |
dc.subject.classification | Fisiologia | - |
dc.subject.classification | Resistència a la insulina | - |
dc.subject.classification | Metabolisme | - |
dc.subject.classification | Inflamació | - |
dc.subject.classification | Reticle endoplasmàtic | - |
dc.subject.classification | Ratolins (Animals de laboratori) | - |
dc.subject.other | Insulin | - |
dc.subject.other | Pharmacology | - |
dc.subject.other | Pharmacokinetics | - |
dc.subject.other | Physiology | - |
dc.subject.other | Insulin resistance | - |
dc.subject.other | Metabolism | - |
dc.subject.other | Inflammation | - |
dc.subject.other | Endoplasmic reticulum | - |
dc.subject.other | Mice (Laboratory animals) | - |
dc.title | The Bace1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 678954 | - |
dc.date.updated | 2020-06-09T09:41:38Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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File | Description | Size | Format | |
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678954.pdf | 2.21 MB | Adobe PDF | View/Open |
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