2024-03-29T12:30:54Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/47272022-04-29T12:02:48Zcom_10259_4725com_10259_5086com_10259_2604col_10259_4726
Leptolide improves insulin resistance in diet-induced obese mice
Villa Pérez, Pablo .
Cueto, Mercedes .
Díaz Marrero, Ana R. .
Lobatón, Carmen D.
Moreno, Alfredo
Perdomo Hernández, Germán M.
Cózar Castellano, Irene
leptolide
insulin resistance
obesity
type 2 diabetes
HepG2 cells
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
2018-02-05T09:32:25Z
2018-02-05T09:32:25Z
2017-09
info:eu-repo/semantics/article
1660-3397
http://hdl.handle.net/10259/4727
10.3390/md15090289
eng
Marine Drugs. 2017, V. 15, n. 9, art. 289
https://doi.org/10.3390/md15090289
info:eu-repo/grantAgreement/JCyL/BIO/VA40/15
info:eu-repo/grantAgreement/MINECO/SAF2014-58702-C2-1-R
info:eu-repo/grantAgreement/MINECO/SAF2014-58702-C2-2-R
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Attribution 4.0 International
MDPI