Weaning Triggers a Maturation Step of Pancreatic β Cells

Miri Stolovich-Rain, Jonatan Enk, Jonas Vikesa, Finn Cilius Nielsen, Ann Saada, Benjamin Glaser, Yuval Dor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Because tissue regeneration deteriorates with age, it is generally assumed that the younger the animal, the better it compensates for tissue damage. We have examined the effect of young age on compensatory proliferation of pancreatic β cells invivo. Surprisingly, β cells in suckling mice fail to enter the cell division cycle in response to a diabetogenic injury or increased glycolysis. The potential of β cells for compensatory proliferation is acquired following premature weaning to normal chow, but not to a diet mimicking maternal milk. In addition, weaning coincides with enhanced glucose-stimulated oxidative phosphorylation and insulin secretion from islets. Transcriptome analysis reveals that weaning increases the expression of genes involved in replication licensing, suggesting a mechanism for increased responsiveness to the mitogenic activity of high glucose. We propose that weaning triggers a discrete maturation step of β cells, elevating both the mitogenic and secretory response to glucose.

Original languageAmerican English
Pages (from-to)535-545
Number of pages11
JournalDevelopmental Cell
Volume32
Issue number5
DOIs
StatePublished - 9 Mar 2015

Bibliographical note

Funding Information:
This work was funded by grants from the β-cell Biology Consortium, JDRF, ERC, EU/FP7 (BetaCellTherapy, grant #241883), the Helmsley Charitable trust, the DON foundation, BIRAX, ISF, and the I-CORE Program of The Israel Science Foundation #41.11 (to Y.D.) and supported in part by a grant from USAID’s American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University Medical School Flow Cytometry laboratory. M.S.-R. was supported by a postdoctoral fellowship from Novo Nordisk. We thank Agnes Klochendler for help with transcriptome analysis, Daniela Dadon for help with GKA experiments, and Michael Brandeis, Yossi Shlomai, Maureen Gannon, and Doris Stoffers for discussions.

Publisher Copyright:
© 2015 Elsevier Inc.

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