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Por favor, use este identificador para citar o enlazar este ítem: http://uvadoc.uva.es/handle/10324/16726
Título: Epoxypukalide induces proliferation and protects against cytokine-mediated apoptosis in primary cultures of pancreatic β-cells
Autor: López-Acosta, José Francisco
Moreno-Amador, José Luis
Jiménez-Palomares, Margarita
Díaz- Marrero, Ana R.
Cueto, Mercedes
Perdomo, Germán
Cózar-Castellano, Irene
Año del Documento: 2013
Editorial: Public Library of Science
Descripción: Producción Científica
Documento Fuente: PLoS ONE, (2013); 8(1): e52862
Resumen: There is an urgency to find new treatments for the devastating epidemic of diabetes. Pancreatic β-cells viability and function are impaired in the two most common forms of diabetes, type 1 and type 2. Regeneration of pancreatic β-cells has been proposed as a potential therapy for diabetes. In a preliminary study, we screened a collection of marine products for β-cell proliferation. One unique compound (epoxypukalide) showed capability to induce β-cell replication in the cell line INS1 832/13 and in primary rat cell cultures. Epoxypukalide was used to study β-cell proliferation by [3H]thymidine incorporation and BrdU incorporation followed by BrdU/insulin staining in primary cultures of rat islets. AKT and ERK1/2 signalling pathways were analyzed. Cell cycle activators, cyclin D2 and cyclin E, were detected by western-blot. Apoptosis was studied by TUNEL and cleaved caspase 3. β-cell function was measured by glucose-stimulated insulin secretion. Epoxypukalide induced 2.5-fold increase in β-cell proliferation; this effect was mediated by activation of ERK1/2 signalling pathway and upregulation of the cell cycle activators, cyclin D2 and cyclin E. Interestingly, epoxypukalide showed protection from basal (40% lower versus control) and cytokine-induced apoptosis (80% lower versus control). Finally, epoxypukalide did not impair β-cell function when measured by glucose-stimulated insulin secretion. In conclusion, epoxypukalide induces β-cell proliferation and protects against basal and cytokine-mediated β-cell death in primary cultures of rat islets. These findings may be translated into new treatments for diabetes
Materias (normalizadas): Diabetes
Células - Reproducción
Pancreas
ISSN: 1932-6203
Revisión por Pares: SI
DOI: 10.1371/journal.pone.0052862
Idioma: eng
URI: http://uvadoc.uva.es/handle/10324/16726
Derechos: info:eu-repo/semantics/openAccess
Aparece en las colecciones:DEP06 - Artículos de revista

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