{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:06:02Z","timestamp":1790042762648,"version":"4.0.1"},"reference-count":48,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK092456"],"award-info":[{"award-number":["R01DK092456"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI116491"],"award-info":[{"award-number":["U19 AI116491"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010327","name":"Cincinnati Children's Research Foundation","doi-asserted-by":"publisher","award":["P30 DKO789392"],"award-info":[{"award-number":["P30 DKO789392"]}],"id":[{"id":"10.13039\/100010327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>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. To do this 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, \u03b2\u2212cell maturation and function was impaired, and animals lost islet mass. Moreover, we discovered these distinct functions of mTOR are mediated by separate downstream branches of the pathway, in that mTORC1 (Raptor) is the main complex mediating maturation and function of islets, whereas mTORC2 (Rictor) impacts islet mass and architecture. Taken together, these findings suggest that nutrient-sensing may be a trigger for postnatal \u03b2 cell maturation and islet development.<\/jats:p>","DOI":"10.1242\/dev.146316","type":"journal-article","created":{"date-parts":[[2017,6,3]],"date-time":"2017-06-03T00:20:20Z","timestamp":1496449220000},"source":"Crossref","is-referenced-by-count":28,"title":["Distinct roles for the mTOR pathway in postnatal morphogenesis, maturation and function of pancreatic islets"],"prefix":"10.1242","author":[{"given":"Katie L.","family":"Sinagoga","sequence":"first","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Stone","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-4382","authenticated-orcid":false,"given":"Jacqueline V.","family":"Schiesser","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie I.","family":"Schweitzer","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leesa","family":"Sampson","sequence":"additional","affiliation":[{"name":"Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1398-848X","authenticated-orcid":false,"given":"James M.","family":"Wells","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"},{"name":"Division of Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042609001157400_DEV146316C1","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1101\/gad.12.12.1763","article-title":"beta-cell-specific inactivation of the mouse Ipf1\/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes","volume":"12","author":"Ahlgren","year":"1998","journal-title":"Genes Dev."},{"key":"2021042609001157400_DEV146316C2","first-page":"691","article-title":"Persistent hyperinsulinemic hypoglycemia of infancy: constitutive activation of the mTOR pathway with associated exocrine-islet transdifferentiation and therapeutic implications","volume":"3","author":"Alexandrescu","year":"2010","journal-title":"Int. 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