Replication Confers β Cell Immaturity

Nat Commun. 2018 Feb 2;9(1):485. doi: 10.1038/s41467-018-02939-0.

Abstract

Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal β cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that β-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult β cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal β that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the β cell reverts to a less functional one in response to proliferative cues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Differentiation / genetics
  • Cell Division / genetics
  • Cell Proliferation / genetics*
  • Gene Expression
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / cytology
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Proto-Oncogene Proteins c-myc / genetics*

Substances

  • Insulin
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc