1. Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells
- Author
-
José Francisco López-Acosta, Jennifer Muñoz-Barrera, Sara Fernández-Luis, Blanca Heras-Pozas, Pablo Villa-Pérez, Irene Cózar-Castellano, Margarita Jimenez-Palomares, Ernesto Bernal-Mizrachi, José Luis Moreno-Amador, Germán Perdomo, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Juvenile Diabetes Research Foundation International, and American Diabetes Association
- Subjects
Male ,Physiology ,Cell Survival ,Endocrinology, Diabetes and Metabolism ,Cellular differentiation ,Cyclin D ,Cyclin A ,Proliferation ,Cyclin B ,Mice, Transgenic ,Cell cycle ,Mice ,Cyclin C ,Physiology (medical) ,Insulin-Secreting Cells ,Animals ,Humans ,Rats, Wistar ,Pancreatic β-cell ,Cells, Cultured ,Cyclin ,Cell Proliferation ,biology ,Cell growth ,Cell Differentiation ,Molecular biology ,3. Good health ,Cell biology ,Rats ,Mice, Inbred C57BL ,biology.protein ,Call for Papers ,Cyclin A2 - Abstract
Activation of pancreatic β-cell proliferation has been proposed as an approach to replace reduced functional β-cell mass in diabetes. Quiescent fibroblasts exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces pancreatic β-cell proliferation. We hypothesized that cyclin C overexpression would induce β-cell proliferation through G0 exit, thus being a potential therapeutic target to recover functional β-cell mass. We used isolated rat and human islets transduced with adenovirus expressing cyclin C. We measured multiple markers of proliferation: [3H]thymidine incorporation, BrdU incorporation and staining, and Ki67 staining. Furthermore, we detected β-cell death by TUNEL, β-cell differentiation by RT-PCR, and β-cell function by glucose-stimulated insulin secretion. Interestingly, we have found that cyclin C increases rat and human β-cell proliferation. This augmented proliferation did not induce β-cell death, dedifferentiation, or dysfunction in rat or human islets. Our results indicate that cyclin C is a potential target for inducing β-cell regeneration., This work was supported by grants from ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, Spain (PS09/00671); Programa Ramón y Cajal (RYC-2011-08101) Ministerio de Economía y Competitividad, Spain; and Europe-FP7 Marie Curie grant (IRG-247835) to I. Cózar-Castellano, by Europe-FP7 Marie Curie grant (IRG-256369) to G. Perdomo, by National Institute of Diabetes and Digestive and Kidney Diseases Grants (RO1-DK-073716;, DK-084236) and Juvenile Diabetes Research Foundation (17-2013-416) to E. Bernal-Mizrachi, and by a Minority Postdoctoral Fellowship from the American Diabetes Association to M. Jiménez-Palomares.
- Published
- 2015