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

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)1-9
Number of pages9
JournalCell Cycle
DOIs
StateAccepted/In press - Oct 5 2017

Fingerprint

Cyclin D2
Regeneration
Cell Self Renewal
Streptozocin
Weaning
Type 1 Diabetes Mellitus

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. (Accepted/In press). Cyclin D2 is sufficient to drive β cell self-renewal and regeneration. Cell Cycle, 1-9. https://doi.org/10.1080/15384101.2017.1319999

Cyclin D2 is sufficient to drive β cell self-renewal and regeneration. / Tschen, Shuen ing; Zeng, Chun; Field, Loren; Dhawan, Sangeeta; Bhushan, Anil; Georgia, Senta.

In: Cell Cycle, 05.10.2017, p. 1-9.

Research output: Contribution to journalArticle

Tschen, Shuen ing ; Zeng, Chun ; Field, Loren ; Dhawan, Sangeeta ; Bhushan, Anil ; Georgia, Senta. / Cyclin D2 is sufficient to drive β cell self-renewal and regeneration. In: Cell Cycle. 2017 ; pp. 1-9.
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