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dc.contributor.authorVilla Pérez, Pablo .
dc.contributor.authorGallardo, Amalia B. .
dc.contributor.authorDíaz Marrero, Ana R. .
dc.contributor.authorRosa, José M. de la .
dc.contributor.authorCroz, Luis D’ .
dc.contributor.authorPerdomo Hernández, Germán M. 
dc.contributor.authorCózar Castellano, Irene
dc.contributor.authorDarias, José .
dc.contributor.authorCueto, Mercedes .
dc.date.accessioned2018-10-15T08:23:37Z
dc.date.available2018-10-15T08:23:37Z
dc.date.issued2018-02
dc.identifier.issn1660-3397
dc.identifier.urihttp://hdl.handle.net/10259/4966
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.sponsorshipMinisterio de Ciencia e Innovación (SAF2009-0839 and RTA 2015-00010-C03-02). ARDM acknowledges funding from IMBRAIN project (FP7-REGPOT-2012-CT2012-31637-IMBRAIN) and from Cabildo de Tenerife (Agustín de Betancourt Programme). A.B.G. would like to thank Convenio Universidad de Magallanes (Chile) and CSIC, project 2009CL0031, for financial support.en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherMDPIen
dc.relation.ispartofMarine Drugs. 2018, V. 16, n. 2, art. 49en
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectLeptogorgiaen
dc.subjectcembranolidesen
dc.subjectfuranocembranolidesen
dc.subjectdiketocembranolidesen
dc.subjectseco-furanocembranolidesen
dc.subjectchloro-furanocembranolidesen
dc.subjectpancreatic beta-cellsen
dc.subject.otherEndocrinologíaes
dc.subject.otherEndocrinologyen
dc.titleChloro-Furanocembranolides from Leptogorgia sp. Improve Pancreatic Beta-Cell Proliferationen
dc.typeinfo:eu-repo/semantics/article
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.relation.publisherversionhttps://doi.org/10.3390/md16020049
dc.identifier.doi10.3390/md16020049
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/SAF2009-0839
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/RTA 2015-00010-C03-02
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/CT2012-31637-IMBRAIN
dc.relation.projectIDinfo:eu-repo/grantAgreement/CSIC/2009CL0031
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersionen


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