Cyclin D2 is sufficient to drive β cell self-renewal and regeneration

Shuen ing Tschen, Chun Zeng, Loren Field, Sangeeta Dhawan, Anil Bhushan, Senta Georgia

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Diabetes results from an inadequate mass of functional β cells, due to either β cell loss caused by autoimmune destruction (type I diabetes) or β cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate β cell mass may be key to developing new techniques that foster β cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal β cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive β cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in β cells, we show that cyclin D2 overexpression increases β cell self-renewal post-weaning and results in increased β cell mass. β cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. β cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive β cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in β cells of cyclin D2−/− mice. Transgenic overexpression of cyclin D2 in cyclin D2 / β cells was sufficient to restore β cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2−/− littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate β cell self-renewal and that manipulation of its expression could be used to enhance β cell regeneration.

Original languageEnglish (US)
Pages (from-to)2183-2191
Number of pages9
JournalCell Cycle
Volume16
Issue number22
DOIs
StatePublished - Nov 17 2017

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Keywords

  • cell cycle
  • cyclin D2
  • diabetes
  • insulin
  • β cell regeneration

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Tschen, S. I., Zeng, C., Field, L., Dhawan, S., Bhushan, A., & Georgia, S. (2017). Cyclin D2 is sufficient to drive β cell self-renewal and regeneration. Cell Cycle, 16(22), 2183-2191. https://doi.org/10.1080/15384101.2017.1319999