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dc.contributor.authorVilla Pérez, Pablo .
dc.contributor.authorCueto, Mercedes .
dc.contributor.authorDíaz Marrero, Ana R. .
dc.contributor.authorLobatón, Carmen D.
dc.contributor.authorMoreno, Alfredo
dc.contributor.authorPerdomo Hernández, Germán M. 
dc.contributor.authorCózar Castellano, Irene
dc.date.accessioned2018-02-05T09:32:25Z
dc.date.available2018-02-05T09:32:25Z
dc.date.issued2017-09
dc.identifier.issn1660-3397
dc.identifier.urihttp://hdl.handle.net/10259/4727
dc.description.abstractType 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity. To this end, we tested the hypothesis that leptolide should protect against fatty acid-induced insulin resistance in hepatocytes. In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two-fold above vehicle-treated HepG2 cells. In addition, leptolide (0.1 µM) counteracted palmitate-induced insulin resistance by augmenting by four-fold insulin-stimulated phosphorylation of PKB in HepG2 cells. In vivo, acute intraperitoneal administration of leptolide (0.1 mg/kg and 1 mg/kg) improved glucose tolerance and insulin sensitivity in lean mice. Likewise, prolonged leptolide treatment (0.1 mg/kg) in diet-induced obese mice improved insulin sensitivity. These effects were paralleled with an ~50% increased of insulin-stimulated phosphorylation of PKB in liver and skeletal muscle and reduced circulating pro-inflammatory cytokines in obese mice. We concluded that leptolide significantly improves insulin sensitivity in vitro and in obese mice, suggesting that leptolide may be another potential treatment for T2DMen
dc.description.sponsorshipSociedad Española de Diabetes (Ayudas Investigación Básica 2014), Salud Castilla y León (BIO/VA40/15) and Ministerio de Economía y Competitividad-Spain (SAF2014-58702-C2-1-R) to I.C. and Ministerio de Economía y Competitividad-Spain (SAF2014-58702-C2-2-R) to G.P.en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherMDPIen
dc.relation.ispartofMarine Drugs. 2017, V. 15, n. 9, art. 289en
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectleptolideen
dc.subjectinsulin resistanceen
dc.subjectobesityen
dc.subjecttype 2 diabetesen
dc.subjectHepG2 cellsen
dc.subject.otherEndocrinologyen
dc.subject.otherEndocrinologíaes
dc.titleLeptolide improves insulin resistance in diet-induced obese miceen
dc.typeinfo:eu-repo/semantics/article
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.relation.publisherversionhttps://doi.org/10.3390/md15090289
dc.identifier.doi10.3390/md15090289
dc.relation.projectIDinfo:eu-repo/grantAgreement/JCyL/BIO/VA40/15
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/SAF2014-58702-C2-1-R
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/SAF2014-58702-C2-2-R
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersionen


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