Leptolide improves insulin resistance in diet-induced obese mice

Villa-Pérez, Pablo; Cueto, Mercedes; Díaz-Marrero, Ana R.; Lobatón, Carmen D.; Moreno, Alfredo; Perdomo, Germán; Cózar-Castellano, Irene; Ministerio de Economía y Competitividad (España)

Leptolide improves insulin resistance in diet-induced obese mice

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

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Bibliographic Details
Main Authors:	Villa-Pérez, Pablo, Cueto, Mercedes, Díaz-Marrero, Ana R., Lobatón, Carmen D., Moreno, Alfredo, Perdomo, Germán, Cózar-Castellano, Irene
Other Authors:	Ministerio de Economía y Competitividad (España)
Format:	artículo biblioteca
Published:	Molecular Diversity Preservation International 2017
Subjects:	HepG2 cells, Insulin resistance, Obesity, Type 2 diabetes, Leptolide,
Online Access:	http://hdl.handle.net/10261/158149 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100003339 http://dx.doi.org/10.13039/501100014180
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id	dig-ipna-es-10261-158149
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spelling	dig-ipna-es-10261-1581492021-12-28T16:03:58Z Leptolide improves insulin resistance in diet-induced obese mice Villa-Pérez, Pablo Cueto, Mercedes Díaz-Marrero, Ana R. Lobatón, Carmen D. Moreno, Alfredo Perdomo, Germán Cózar-Castellano, Irene Ministerio de Economía y Competitividad (España) Junta de Castilla y León Fundación de la Sociedad Española de Diabetes Consejo Superior de Investigaciones Científicas (España) HepG2 cells Insulin resistance Obesity Type 2 diabetes Leptolide This 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 T2DM This 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 Reviewed 2017-12-13T10:51:01Z 2017-12-13T10:51:01Z 2017 2017-12-13T10:51:01Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.3390/md15090289 issn: 1660-3397 Marine Drugs 15(9): 2889 (2017) http://hdl.handle.net/10261/158149 10.3390/md15090289 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100003339 http://dx.doi.org/10.13039/501100014180 28914811 #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-R info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-58702-C2-1-R Publisher's version Sí open Molecular Diversity Preservation International
institution	IPNA ES
collection	DSpace
country	España
countrycode	ES
component	Bibliográfico
access	En linea
databasecode	dig-ipna-es
tag	biblioteca
region	Europa del Sur
libraryname	Biblioteca del IPNA España
topic	HepG2 cells Insulin resistance Obesity Type 2 diabetes Leptolide HepG2 cells Insulin resistance Obesity Type 2 diabetes Leptolide
spellingShingle	HepG2 cells Insulin resistance Obesity Type 2 diabetes Leptolide HepG2 cells Insulin resistance Obesity Type 2 diabetes Leptolide Villa-Pérez, Pablo Cueto, Mercedes Díaz-Marrero, Ana R. Lobatón, Carmen D. Moreno, Alfredo Perdomo, Germán Cózar-Castellano, Irene Leptolide improves insulin resistance in diet-induced obese mice
description	This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017.
author2	Ministerio de Economía y Competitividad (España)
author_facet	Ministerio de Economía y Competitividad (España) Villa-Pérez, Pablo Cueto, Mercedes Díaz-Marrero, Ana R. Lobatón, Carmen D. Moreno, Alfredo Perdomo, Germán Cózar-Castellano, Irene
format	artículo
topic_facet	HepG2 cells Insulin resistance Obesity Type 2 diabetes Leptolide
author	Villa-Pérez, Pablo Cueto, Mercedes Díaz-Marrero, Ana R. Lobatón, Carmen D. Moreno, Alfredo Perdomo, Germán Cózar-Castellano, Irene
author_sort	Villa-Pérez, Pablo
title	Leptolide improves insulin resistance in diet-induced obese mice
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
publisher	Molecular Diversity Preservation International
publishDate	2017
url	http://hdl.handle.net/10261/158149 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100003339 http://dx.doi.org/10.13039/501100014180
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_version_	1777669730482520064

Leptolide improves insulin resistance in diet-induced obese mice

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