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 Citations (Scopus)

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

Fingerprint

Cyclin C
Cell Proliferation
Cell Death
Cell Dedifferentiation
Cyclin D2
Staining and Labeling
Cyclin E
Cyclin D1
In Situ Nick-End Labeling
Bromodeoxyuridine
Adenoviridae
Thymidine
Regeneration
Cell Differentiation
Fibroblasts
Phosphorylation
Insulin
Glucose
Polymerase Chain Reaction

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., ... 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

Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells. / Jiménez-Palomares, Margarita; López-Acosta, José Francisco; Villa-Pérez, Pablo; Moreno-Amador, José Luis; Muñoz-Barrera, Jennifer; Fernández-Luis, Sara; Heras-Pozas, Blanca; Perdomo, Germán; Bernal Mizrachi, Ernesto; Cózar-Castellano, Irene.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 308, No. 6, 15.03.2015, p. E450-E459.

Research output: Contribution to journalArticle

Jiménez-Palomares, M, López-Acosta, JF, Villa-Pérez, P, Moreno-Amador, JL, 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, vol. 308, no. 6, pp. E450-E459. https://doi.org/10.1152/ajpendo.00260.2014
Jiménez-Palomares M, López-Acosta JF, Villa-Pérez P, Moreno-Amador JL, Muñoz-Barrera J, Fernández-Luis S et al. Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells. American Journal of Physiology - Endocrinology and Metabolism. 2015 Mar 15;308(6):E450-E459. https://doi.org/10.1152/ajpendo.00260.2014
Jiménez-Palomares, Margarita ; López-Acosta, José Francisco ; Villa-Pérez, Pablo ; Moreno-Amador, José Luis ; Muñoz-Barrera, Jennifer ; Fernández-Luis, Sara ; Heras-Pozas, Blanca ; Perdomo, Germán ; Bernal Mizrachi, Ernesto ; Cózar-Castellano, Irene. / Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells. In: American Journal of Physiology - Endocrinology and Metabolism. 2015 ; Vol. 308, No. 6. pp. E450-E459.
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