Distinct roles for the mTOR pathway in postnatal morphogenesis, maturation and function of pancreatic islets.

Sinagoga KL, Stone WJ, Schiesser JV, Schweitzer JI, Sampson L, Zheng Y, Wells JM
Development. 2017 144 (13): 2402-2414

PMID: 28576773 · PMCID: PMC5536865 · DOI:10.1242/dev.146316

While much is known about the molecular pathways that regulate embryonic development and adult homeostasis of the endocrine pancreas, little is known about what regulates early postnatal development and maturation of islets. Given that birth marks the first exposure to enteral nutrition, we investigated how nutrient-regulated signaling pathways influence postnatal islet development in mice. We performed loss-of-function studies of mechanistic target of rapamycin (mTOR), a highly conserved kinase within a nutrient-sensing pathway known to regulate cellular growth, morphogenesis and metabolism. Deletion of Mtor in pancreatic endocrine cells had no significant effect on their embryonic development. However, within the first 2 weeks after birth, mTOR-deficient islets became dysmorphic, β-cell maturation and function were impaired, and animals lost islet mass. Moreover, we discovered that these distinct functions of mTOR are mediated by separate downstream branches of the pathway, in that mTORC1 (with adaptor protein Raptor) is the main complex mediating the maturation and function of islets, whereas mTORC2 (with adaptor protein Rictor) impacts islet mass and architecture. Taken together, these findings suggest that nutrient sensing may be an essential trigger for postnatal β-cell maturation and islet development.

© 2017. Published by The Company of Biologists Ltd.

MeSH Terms (13)

Animals Animals, Newborn Cell Aggregation Islets of Langerhans Mechanistic Target of Rapamycin Complex 1 Mechanistic Target of Rapamycin Complex 2 Mice Models, Biological Morphogenesis Multiprotein Complexes Mutation Signal Transduction TOR Serine-Threonine Kinases

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