RT info:eu-repo/semantics/article
T1 Leptolide improves insulin resistance in diet-induced obese mice
A1 Villa Pérez, Pablo .
A1 Cueto, Mercedes .
A1 Díaz Marrero, Ana R. .
A1 Lobatón, Carmen D.
A1 Moreno, Alfredo
A1 Perdomo Hernández, Germán M.
A1 Cózar Castellano, Irene
K1 leptolide
K1 insulin resistance
K1 obesity
K1 type 2 diabetes
K1 HepG2 cells
K1 Endocrinology
K1 Endocrinología
AB 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
PB MDPI
SN 1660-3397
YR 2017
FD 2017-09
LK http://hdl.handle.net/10259/4727
UL http://hdl.handle.net/10259/4727
LA eng
NO Sociedad Española de Diabetes (Ayudas InvestigaciónBásica 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) toG.P.
DS Repositorio Institucional de la Universidad de Burgos
RD 22-nov-2024