RT journal article
T1 Epoxypukalide Induces Proliferation and Protects against Cytokine-Mediated Apoptosis in Primary Cultures of Pancreatic β-Cells
A1 Lopez-Acosta, José Francisco
A1 Moreno-Amador, José Luis
A1 Jiménez Palomares, Margarita
A1 Diaz-Marrero, Ana R.
A1 Cueto, Mercedes
A1 Perdomo, Germán
A1 Cozar-Castellano, Irene
A2 BiomedicinaBiotecnología y Salud Pública
K1 CYCLIN D2
K1 REPLICATION
K1 MOLECULE
K1 GROWTH
K1 INFLAMMATION
K1 EXPRESSION
K1 EXPANSION
K1 HUMANS
K1 MICE
K1 MASS
AB There is an urgency to find new treatments for the devastating epidemic of diabetes. Pancreatic beta-cells viability and function are impaired in the two most common forms of diabetes, type 1 and type 2. Regeneration of pancreatic beta-cells has been proposed as a potential therapy for diabetes. In a preliminary study, we screened a collection of marine products for beta-cell proliferation. One unique compound (epoxypukalide) showed capability to induce beta-cell replication in the cell line INS1 832/13 and in primary rat cell cultures. Epoxypukalide was used to study beta-cell proliferation by [H-3] 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. beta-cell function was measured by glucose-stimulated insulin secretion. Epoxypukalide induced 2.5-fold increase in beta-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 beta-cell function when measured by glucose-stimulated insulin secretion. In conclusion, epoxypukalide induces beta-cell proliferation and protects against basal and cytokine-mediated beta-cell death in primary cultures of rat islets. These findings may be translated into new treatments for diabetes.
PB Plos One
YR 2013
FD 2013-01-02
LK http://hdl.handle.net/10498/34803
UL http://hdl.handle.net/10498/34803
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026