2026-05-06T16:59:31Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/47272022-04-29T12:02:48Zcom_10259_4725com_10259_5086com_10259_2604col_10259_4726

Villa Pérez, Pablo . 3513e97f-2ba9-4b82-a9b1-325531b44fc3 500 Cueto, Mercedes . 3bcde508-86c0-472f-ad4c-8ece1cb64c13 500 Díaz Marrero, Ana R. . 2e0cd7df-835d-434b-a151-c62f8678289b 500 Lobatón, Carmen D. 34ae5e7d-c828-4fae-a691-eb28cce143b7 500 Moreno, Alfredo 92809a8e-4bc4-4f5f-a226-66743932a929 500 Perdomo Hernández, Germán M. 433 500 Cózar Castellano, Irene 3f72cbc3-d322-4e0a-a780-4e0fc4965813 500 2018-02-05T09:32:25Z 2018-02-05T09:32:25Z 2017-09 1660-3397 http://hdl.handle.net/10259/4727 10.3390/md15090289 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 Sociedad Española de Diabetes (Ayudas Investigación Básica 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) to G.P. application/pdf eng MDPI 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 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess leptolide insulin resistance obesity type 2 diabetes HepG2 cells Endocrinology Endocrinología Leptolide improves insulin resistance in diet-induced obese mice info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/4727/8/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 8 THUMBNAIL Villa-MD_2017.pdf.jpg Villa-MD_2017.pdf.jpg IM Thumbnail image/jpeg 3131 https://riubu.ubu.es/bitstream/10259/4727/7/Villa-MD_2017.pdf.jpg f4d86caf6da7e95bd0719218c63180f2 MD5 7 ORIGINAL Villa-MD_2017.pdf Villa-MD_2017.pdf application/pdf 1404859 https://riubu.ubu.es/bitstream/10259/4727/1/Villa-MD_2017.pdf 977376d7fcaa530740a60427a0d97ff6 MD5 1 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/4727/5/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 5 TEXT Villa-MD_2017.pdf.txt Villa-MD_2017.pdf.txt Extracted text text/plain 58874 https://riubu.ubu.es/bitstream/10259/4727/6/Villa-MD_2017.pdf.txt 4c22e999d70afb82c39e99ad9a558af0 MD5 6 10259/4727 oai:riubu.ubu.es:10259/4727 2022-04-29 14:02:48.402 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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