Leptolide improves insulin resistance in diet-induced obese mice

This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017.

Detalles Bibliográficos
Autores: Villa-Pérez, Pablo, Cueto, Mercedes, Díaz-Marrero, Ana Raquel, Lobatón, Carmen D., Moreno, Alfredo, Perdomo, Germán, Cózar-Castellano, Irene
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/158149
Acceso en línea:http://hdl.handle.net/10261/158149
Access Level:acceso abierto
Palabra clave:HepG2 cells
Insulin resistance
Obesity
Type 2 diabetes
Leptolide
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spelling Leptolide improves insulin resistance in diet-induced obese miceVilla-Pérez, PabloCueto, MercedesDíaz-Marrero, Ana RaquelLobatón, Carmen D.Moreno, AlfredoPerdomo, GermánCózar-Castellano, IreneHepG2 cellsInsulin resistanceObesityType 2 diabetesLeptolideThis article belongs to the Special Issue Marine Compounds and Inflammation II, 2017.Type 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 T2DMThis research has been funded by Sociedad 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.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer ReviewedMolecular Diversity Preservation InternationalMinisterio de Economía y Competitividad (España)Junta de Castilla y LeónFundación de la Sociedad Española de DiabetesConsejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720172017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/158149reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-58702-C2-2-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-58702-C2-1-RSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1581492026-05-22T06:33:51Z
dc.title.none.fl_str_mv Leptolide improves insulin resistance in diet-induced obese mice
title Leptolide improves insulin resistance in diet-induced obese mice
spellingShingle Leptolide improves insulin resistance in diet-induced obese mice
Villa-Pérez, Pablo
HepG2 cells
Insulin resistance
Obesity
Type 2 diabetes
Leptolide
title_short Leptolide improves insulin resistance in diet-induced obese mice
title_full Leptolide improves insulin resistance in diet-induced obese mice
title_fullStr Leptolide improves insulin resistance in diet-induced obese mice
title_full_unstemmed Leptolide improves insulin resistance in diet-induced obese mice
title_sort Leptolide improves insulin resistance in diet-induced obese mice
dc.creator.none.fl_str_mv Villa-Pérez, Pablo
Cueto, Mercedes
Díaz-Marrero, Ana Raquel
Lobatón, Carmen D.
Moreno, Alfredo
Perdomo, Germán
Cózar-Castellano, Irene
author Villa-Pérez, Pablo
author_facet Villa-Pérez, Pablo
Cueto, Mercedes
Díaz-Marrero, Ana Raquel
Lobatón, Carmen D.
Moreno, Alfredo
Perdomo, Germán
Cózar-Castellano, Irene
author_role author
author2 Cueto, Mercedes
Díaz-Marrero, Ana Raquel
Lobatón, Carmen D.
Moreno, Alfredo
Perdomo, Germán
Cózar-Castellano, Irene
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Junta de Castilla y León
Fundación de la Sociedad Española de Diabetes
Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv HepG2 cells
Insulin resistance
Obesity
Type 2 diabetes
Leptolide
topic HepG2 cells
Insulin resistance
Obesity
Type 2 diabetes
Leptolide
description This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/158149
url http://hdl.handle.net/10261/158149
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
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info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-58702-C2-2-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-58702-C2-1-R
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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