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Replication confers ? cell immaturity.

ABSTRACT: Pancreatic ? cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in ?-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal ? cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that ?-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult ? cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal ? 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 ? cell reverts to a less functional one in response to proliferative cues.

SUBMITTER: Puri S

PROVIDER: S-EPMC5797102 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Replication confers β cell immaturity.

Puri Sapna S Roy Nilotpal N Russ Holger A HA Leonhardt Laura L French Esra K EK Roy Ritu R Bengtsson Henrik H Scott Donald K DK Stewart Andrew F AF Hebrok Matthias M

Nature communications 20180202 1

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 cel ...[more]

PMID: 29396395

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