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Epoxypukalide induces proliferation and protects against cytokine-mediated apoptosis in primary cultures of pancreatic β-cells

AuthorsLópez-Acosta, José Francisco CSIC; Moreno-Amador, José Luis; Jiménez-Palomares, Margarita; Díaz-Marrero, Ana R. CSIC ORCID; Cueto, Mercedes CSIC ORCID ; Perdomo, Germán; Cózar-Castellano, Irene CSIC ORCID CVN
Issue Date2013
PublisherPublic Library of Science
CitationPLoS ONE 8(1): e52862 (2013)
AbstractThere is an urgency to find new treatments for the devastating epidemic of diabetes. Pancreatic b-cells viability and function are impaired in the two most common forms of diabetes, type 1 and type 2. Regeneration of pancreatic b-cells has been proposed as a potential therapy for diabetes. In a preliminary study, we screened a collection of marine products for b-cell proliferation. One unique compound (epoxypukalide) showed capability to induce b-cell replication in the cell line INS1 832/ 13 and in primary rat cell cultures. Epoxypukalide was used to study b-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. b-cell function was measured by glucose-stimulated insulin secretion. Epoxypukalide induced 2.5- fold increase in b-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 b-cell function when measured by glucose-stimulated insulin secretion. In conclusion, epoxypukalide induces b-cell proliferation and protects against basal and cytokine-mediated b-cell death in primary cultures of rat islets. These findings may be translated into new treatments for diabetes. © 2013 López-Acosta et al.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.
Publisher version (URL)
Identifiersdoi: 10.1371/journal.pone.0052862
issn: 1932-6203
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(IPNA) Artículos

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