Replication confers β cell immaturity

Sapna Puri, Nilotpal Roy, Holger A. Russ, Laura Leonhardt, Esra K. French, Ritu Roy, Henrik Bengtsson, Donald K. Scott, Andrew F. Stewart, Matthias Hebrok

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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.

Original languageEnglish
Article number485
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

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