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ArtikelGeneration of functional insulin-producing cells in the gut by Foxo1 ablation  
Oleh: Talchai, Chutima ; Shouhong, Xuan ; Kitamura, Tadahiro
Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 44 no. 04 (Apr. 2012), page 406–412.
Ketersediaan
  • Perpustakaan FK
    • Nomor Panggil: N12.K.2012.01
    • Non-tandon: 1 (dapat dipinjam: 0)
    • Tandon: tidak ada
    Lihat Detail Induk
Isi artikelRestoration 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 ß 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 ß-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.
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