2024-03-29T06:45:59Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/167262021-06-23T09:52:05Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
López Acosta, José Francisco
Moreno Amador, José Luis
Jiménez Palomares, Margarita
Díaz Marrero, Ana R.
Cueto, Mercedes
Perdomo Hernández, Germán
Cózar Castellano, Irene
2016-04-11T08:15:07Z
2016-04-11T08:15:07Z
2013
PLoS ONE, (2013); 8(1): e52862
1932-6203
http://uvadoc.uva.es/handle/10324/16726
10.1371/journal.pone.0052862
e52862
1
PLoS One.
8
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
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
Attribution-NonCommercial-NoDerivatives 4.0 International
Diabetes
Células - Reproducción
Pancreas
Epoxypukalide induces proliferation and protects against cytokine-mediated apoptosis in primary cultures of pancreatic β-cells
info:eu-repo/semantics/article