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Title

Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells

AuthorsJiménez-Palomares, Margarita; López-Acosta, José Francisco CSIC; Villa-Pérez, Pablo; Moreno-Amador, José Luis; Muñoz-Barrera, Jennifer; Fernández-Luis, Sara; Heras-Pozas, Blanca; Perdomo, Germán; Bernal-Mizrachi, Ernesto; Cózar-Castellano, Irene CSIC ORCID CVN
KeywordsCell cycle
Pancreatic β-cell
Cyclin C
Proliferation
Issue Date2015
PublisherAmerican Physiological Society
CitationAJP - Endocrinology and Metabolism 308(6): E450-E459 (2015)
AbstractActivation 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.
Publisher version (URL)https://doi.org/10.1152/ajpendo.00260.2014
URIhttp://hdl.handle.net/10261/157666
DOI10.1152/ajpendo.00260.2014
Identifiersdoi: 10.1152/ajpendo.00260.2014
e-issn: 1522-1555
issn: 0193-1849
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