A Nutrient-Sensing Transition at Birth Triggers Glucose-Responsive Insulin Secretion

Aharon Helman, Andrew L. Cangelosi, Jeffrey C. Davis, Quan Pham, Arielle Rothman, Aubrey L. Faust, Juerg R. Straubhaar, David M. Sabatini, Douglas A. Melton

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


A drastic transition at birth, from constant maternal nutrient supply in utero to intermittent postnatal feeding, requires changes in the metabolic system of the neonate. Despite their central role in metabolic homeostasis, little is known about how pancreatic β cells adjust to the new nutritional challenge. Here, we find that after birth β cell function shifts from amino acid- to glucose-stimulated insulin secretion in correlation with the change in the nutritional environment. This adaptation is mediated by a transition in nutrient sensitivity of the mTORC1 pathway, which leads to intermittent mTORC1 activity. Disrupting nutrient sensitivity of mTORC1 in mature β cells reverts insulin secretion to a functionally immature state. Finally, manipulating nutrient sensitivity of mTORC1 in stem cell-derived β cells in vitro strongly enhances their glucose-responsive insulin secretion. These results reveal a mechanism by which nutrients regulate β cell function, thereby enabling a metabolic adaptation for the newborn.

Original languageAmerican English
Pages (from-to)1004-1016
Number of pages13
JournalCell Metabolism
Issue number5
StatePublished - 5 May 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
Published by Elsevier Inc.


  • embryo
  • in vitro differentiation
  • insulin secretion
  • mTORC1
  • maturation
  • nutrient sensing
  • pancreas
  • stem cell-derived β cells
  • β cells


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