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• W2036682769 abstract "Restoration of regulated insulin secretion is the ultimate goal of therapy for type 1 diabetes. Here, we show that, unexpectedly, somatic ablation of Foxo1 in Neurog3(+) enteroendocrine progenitor cells gives rise to gut insulin-positive (Ins(+)) cells that express markers of mature β cells and secrete bioactive insulin as well as C-peptide in response to glucose and sulfonylureas. Lineage tracing experiments showed that gut Ins(+) cells arise cell autonomously from Foxo1-deficient cells. Inducible Foxo1 ablation in adult mice also resulted in the generation of gut Ins(+) cells. Following ablation by the β-cell toxin streptozotocin, gut Ins(+) cells regenerate and produce insulin, reversing hyperglycemia in mice. The data indicate that Neurog3(+) enteroendocrine progenitors require active Foxo1 to prevent differentiation into Ins(+) cells. Foxo1 ablation in gut epithelium may provide an approach to restore insulin production in type 1 diabetes." @default.
• W2036682769 created "2016-06-24" @default.
• W2036682769 creator A5008120994 @default.
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• W2036682769 date "2012-03-11" @default.
• W2036682769 modified "2023-10-03" @default.
• W2036682769 title "Generation of functional insulin-producing cells in the gut by Foxo1 ablation" @default.
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• W2036682769 doi "https://doi.org/10.1038/ng.2215" @default.
• W2036682769 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3315609" @default.
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