RT info:eu-repo/semantics/article
T1 Leptolide improves insulin resistance in diet-induced obese mice
A1 Cueto, Mercedes
A1 Díaz Marrero, Ana R.
A1 Domínguez Lobatón, María Carmen
A1 Moreno Díaz-Calderón, Alfredo
A1 Perdomo Hernández, Germán
A1 Cózar Castellano, Irene
A1 Villa Pérez, Pablo
K1 Leptolide
K1 Insulin resistance
K1 Obesity
K1 Type 2 diabetes
K1 HepG2 cells
K1 32 Ciencias Médicas
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
YR 2017
FD 2017
LK https://uvadoc.uva.es/handle/10324/56879
UL https://uvadoc.uva.es/handle/10324/56879
LA eng
NO Marine Drugs, 2017, vol. 15, n. 9, p.289
NO Producción Científica
DS UVaDOC
RD 24-nov-2024