2024-03-28T21:22:40Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/49662021-11-10T09:38:25Zcom_10259_4725com_10259_5086com_10259_2604col_10259_4726
Chloro-Furanocembranolides from Leptogorgia sp. Improve Pancreatic Beta-Cell Proliferation
Villa Pérez, Pablo .
Gallardo, Amalia B. .
Díaz Marrero, Ana R. .
Rosa, José M. de la .
Croz, Luis D’ .
Perdomo Hernández, Germán M.
Cózar Castellano, Irene
Darias, José .
Cueto, Mercedes .
Leptogorgia
cembranolides
furanocembranolides
diketocembranolides
seco-furanocembranolides
chloro-furanocembranolides
pancreatic beta-cells
Endocrinología
Endocrinology
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
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.
2018-10-15T08:23:37Z
2018-10-15T08:23:37Z
2018-02
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
1660-3397
http://hdl.handle.net/10259/4966
10.3390/md16020049
eng
Marine Drugs. 2018, V. 16, n. 2, art. 49
https://doi.org/10.3390/md16020049
info:eu-repo/grantAgreement/MINECO/SAF2009-0839
info:eu-repo/grantAgreement/MINECO/RTA 2015-00010-C03-02
info:eu-repo/grantAgreement/EC/FP7/CT2012-31637-IMBRAIN
info:eu-repo/grantAgreement/CSIC/2009CL0031
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
application/pdf
MDPI
https://riubu.ubu.es/bitstream/10259/4966/7/Gallardo-md_2018.pdf.jpg
Hispana
TEXT
http://creativecommons.org/licenses/by/4.0/
RIUBU. Repositorio Institucional de la Universidad de Burgos
http://hdl.handle.net/10259/4966