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Epoxypukalide induces proliferation and protects against cytokine-mediated apoptosis in primary cultures of pancreatic β-cells
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, PLoS ONE, Vol 8, Iss 1, p e52862 (2013), PLoS ONE, UVaDOC. Repositorio Documental de la Universidad de Valladolid
- Publication Year :
- 2013
- Publisher :
- Public Library of Science, 2013.
-
Abstract
- This is an open-access article distributed under the terms of the Creative Commons Attribution License.<br />There 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.<br />This work was supported by ISCIII-Subdireccion Geeneral de Evaluacion y Fomento de la Investigacion, Spain (PS09/00671 and CP08/00094), Europe-FP7 Marie Curie grant (IRG-247835) and Servicio Andaluz de Salud (PI-0256/2009).
- Subjects :
- Cyclin E
lcsh:Medicine
ComputingMilieux_LEGALASPECTSOFCOMPUTING
Apoptosis
Signal transduction
ERK signaling cascade
Biochemistry
Lactones
0302 clinical medicine
Molecular cell biology
Endocrinology
Akt signaling cascade
Insulin-Secreting Cells
Drug Discovery
Insulin
lcsh:Science
Cyclin
0303 health sciences
Multidisciplinary
Cell Death
Células - Reproducción
Cell Cycle
Diabetes
Signaling cascades
Cell cycle
Anthozoa
3. Good health
Medicine
Cytokines
Research Article
medicine.medical_specialty
Drugs and Devices
Drug Research and Development
Immunology
030209 endocrinology & metabolism
Biology
Cell Growth
Cell Line
Diabetes Mellitus, Experimental
03 medical and health sciences
Cyclin D2
Downregulation and upregulation
Internal medicine
medicine
Animals
Hypoglycemic Agents
Rats, Wistar
Immunoassays
Protein kinase B
Pancreas
030304 developmental biology
Cell Proliferation
Diabetic Endocrinology
Dose-Response Relationship, Drug
Cell growth
lcsh:R
Diabetes Mellitus Type 1
Diabetes Mellitus Type 2
Rats
Small Molecules
Cancer research
Immunologic Techniques
lcsh:Q
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, PLoS ONE, Vol 8, Iss 1, p e52862 (2013), PLoS ONE, UVaDOC. Repositorio Documental de la Universidad de Valladolid
- Accession number :
- edsair.doi.dedup.....7107f91dfe0f104ae7bc973ccaf5bcc6