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MRNA sequencing of stem cell-derived beta cells

ABSTRACT: A drastic transition at birth, from constant maternal nutrient supply in utero to intermittent postnatal feeding, requires changes in the metabolic system. Despite their central role in metabolic homeostasis, little is known about how pancreatic beta cells adjust to the new nutritional program. Our experiments show that after birth beta cells shift from amino acid- to glucose-stimulated insulin secretion that correlates with the nutritional environment of the animal. This metabolic adaptation is mediated by a transition in nutrient sensitivity of the mTORC1 pathway , which leads toresults in intermittent mTORC1 signaling activity. Disrupting nutrient sensitivity of mTORC1 in mature beta cells affects insulin secretion and reverts them to an immature functional state. Finally, manipulating nutrient sensitivity of mTORC1 in stem cell-derived beta cells in vitro strongly enhances their glucose-responsive insulin secretion. These results reveal a mechanism by which nutrient sensing regulates beta cell function, thereby enabling a metabolic adaptation for the newborn.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147347 | GEO | 2020/05/07

REPOSITORIES: GEO

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mRNA sequencing of stem cell-derived beta cells before and after transplantation in mice

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