%0 Journal Article
%T Epoxypukalide Induces Proliferation and Protects against Cytokine-Mediated Apoptosis in Primary Cultures of Pancreatic 汕-Cells
%A Jos谷 Francisco L車pez-Acosta
%A Jos谷 Luis Moreno-Amador
%A Margarita Jim谷nez-Palomares
%A Ana R. D赤az-Marrero
%A Mercedes Cueto
%A Germ芍n Perdomo
%A Irene C車zar-Castellano
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0052862
%X There is an urgency to find new treatments for the devastating epidemic of diabetes. Pancreatic 汕-cells viability and function are impaired in the two most common forms of diabetes, type 1 and type 2. Regeneration of pancreatic 汕-cells has been proposed as a potential therapy for diabetes. In a preliminary study, we screened a collection of marine products for 汕-cell proliferation. One unique compound (epoxypukalide) showed capability to induce 汕-cell replication in the cell line INS1 832/13 and in primary rat cell cultures. Epoxypukalide was used to study 汕-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. 汕-cell function was measured by glucose-stimulated insulin secretion. Epoxypukalide induced 2.5-fold increase in 汕-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 汕-cell function when measured by glucose-stimulated insulin secretion. In conclusion, epoxypukalide induces 汕-cell proliferation and protects against basal and cytokine-mediated 汕-cell death in primary cultures of rat islets. These findings may be translated into new treatments for diabetes.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052862