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

Margarita Jiménez-Palomares, José Francisco López-Acosta, Pablo Villa-Pérez, José Luis Moreno-Amador, Jennifer Muñoz-Barrera, Sara Fernández-Luis, Blanca Heras-Pozas, Germán Perdomo, Ernesto Bernal Mizrachi, Irene Cózar-Castellano

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E450-E459
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume308
Issue number6
DOIs
StatePublished - Mar 15 2015
Externally publishedYes

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Keywords

  • Cell cycle
  • Cyclin C
  • Pancreatic β-cell
  • Proliferation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Jiménez-Palomares, M., López-Acosta, J. F., Villa-Pérez, P., Moreno-Amador, J. L., Muñoz-Barrera, J., Fernández-Luis, S., Heras-Pozas, B., Perdomo, G., Bernal Mizrachi, E., & Cózar-Castellano, I. (2015). Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells. American Journal of Physiology - Endocrinology and Metabolism, 308(6), E450-E459. https://doi.org/10.1152/ajpendo.00260.2014