RT info:eu-repo/semantics/article
T1 Chloro-Furanocembranolides from Leptogorgia sp. Improve Pancreatic Beta-Cell Proliferation
A1 Villa Pérez, Pablo .
A1 Gallardo, Amalia B. .
A1 Díaz Marrero, Ana R. .
A1 Rosa, José M. de la .
A1 Croz, Luis D’ .
A1 Perdomo Hernández, Germán M.
A1 Cózar Castellano, Irene
A1 Darias, José .
A1 Cueto, Mercedes .
K1 Leptogorgia
K1 cembranolides
K1 furanocembranolides
K1 diketocembranolides
K1 seco-furanocembranolides
K1 chloro-furanocembranolides
K1 pancreatic beta-cells
K1 Endocrinología
K1 Endocrinology
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 2018
FD 2018-02
LK http://hdl.handle.net/10259/4966
UL http://hdl.handle.net/10259/4966
LA eng
NO Ministerio de Ciencia e Innovación(SAF2009-0839 and RTA 2015-00010-C03-02). ARDM acknowledges funding from IMBRAIN project(FP7-REGPOT-2012-CT2012-31637-IMBRAIN) and from Cabildo de Tenerife (Agustín de Betancourt Programme).A.B.G. would like to thank Convenio Universidad de Magallanes (Chile) and CSIC, project 2009CL0031,for financial support.
DS Repositorio Institucional de la Universidad de Burgos
RD 18-abr-2024