2026-04-29T20:04:07Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/49662021-11-10T09:38:25Zcom_10259_4725com_10259_5086com_10259_2604col_10259_4726

Villa Pérez, Pablo . 3513e97f-2ba9-4b82-a9b1-325531b44fc3 500 Gallardo, Amalia B. . ea1407ce-d434-4063-bc99-a4d502bfc8c5 500 Díaz Marrero, Ana R. . 2e0cd7df-835d-434b-a151-c62f8678289b 500 Rosa, José M. de la . 00acdb77-3cb8-4019-8fbe-862dc003a337 500 Croz, Luis D’ . 153bb50a-d1f7-4cde-a572-fc8751722585 500 Perdomo Hernández, Germán M. 433 500 Cózar Castellano, Irene 3f72cbc3-d322-4e0a-a780-4e0fc4965813 500 Darias, José . 544fa38f-707c-48d7-95d5-410fd62f8c16 500 Cueto, Mercedes . 3bcde508-86c0-472f-ad4c-8ece1cb64c13 500 2018-10-15T08:23:37Z 2018-10-15T08:23:37Z 2018-02 1660-3397 http://hdl.handle.net/10259/4966 10.3390/md16020049 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. application/pdf eng MDPI 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 Leptogorgia cembranolides furanocembranolides diketocembranolides seco-furanocembranolides chloro-furanocembranolides pancreatic beta-cells Endocrinología Endocrinology Chloro-Furanocembranolides from Leptogorgia sp. 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