RT info:eu-repo/semantics/article
T1 Epoxypukalide induces proliferation and protects against cytokine-mediated apoptosis in primary cultures of pancreatic β-cells
A1 López Acosta, José Francisco
A1 Moreno Amador, José Luis
A1 Jiménez Palomares, Margarita
A1 Díaz Marrero, Ana R.
A1 Cueto, Mercedes
A1 Perdomo Hernández, Germán
A1 Cózar Castellano, Irene
K1 Diabetes
K1 Células - Reproducción
K1 Pancreas
AB 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
PB Public Library of Science
SN 1932-6203
YR 2013
FD 2013
LK http://uvadoc.uva.es/handle/10324/16726
UL http://uvadoc.uva.es/handle/10324/16726
LA eng
NO PLoS ONE, (2013); 8(1): e52862
NO Producción Científica
DS UVaDOC
RD 24-nov-2024