ArticleDevelopment (Cambridge, England)2017
Distinct roles for the mTOR pathway in postnatal morphogenesis, maturation and function of pancreatic islets.
Article in Development (Cambridge, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Fetal growth is driven by a bimodal fetal beta cell response and reshaped by a ketogenic diet in a mouse model of maternal diabetes.Diabetologia · 2026Article
- Rab24 protein levels show dynamic changes in mouse tissues and human cancers.Cell and tissue research · 2026Article
- Review
- Peripheral tissular analysis of rapamycin's effect as a neuroprotective agent in vivo.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Novel roles of mTORC2 in regulation of insulin secretion by actin filament remodeling.American journal of physiology. Endocrinology and metabolism · 2022Article
- Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.Nature biotechnology · 2022Article
- Maturation of beta cells: lessons from in vivo and in vitro models.Diabetologia · 2022Review
- Review
- Mechanisms Underlying the Expansion and Functional Maturation of β-Cells in Newborns: Impact of the Nutritional Environment.International journal of molecular sciences · 2022Review
- Engineering islets from stem cells for advanced therapies of diabetes.Nature reviews. Drug discovery · 2021Review
- Reduced synchroneity of intra-islet CaeLife · 2021Article
- The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass.Scientific reports · 2021Article
- Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases.Frontiers in medicine · 2021Review
- Article
- A Nutrient-Sensing Transition at Birth Triggers Glucose-Responsive Insulin Secretion.Cell metabolism · 2020Article
- Inhibition of mTOR Signaling Enhances Maturation of Cardiomyocytes Derived From Human-Induced Pluripotent Stem Cells via p53-Induced Quiescence.Circulation · 2020Article
- Nutrient Sensor mTOR and OGT: Orchestrators of Organelle Homeostasis in PancreaticJournal of diabetes research · 2020Review
- Human stem cell models: lessons for pancreatic development and disease.Genes & development · 2019Review
- β-Cell Maturation and Identity in Health and Disease.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.