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- 학술저널
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- 2017.1
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α-cells, which synthesize glucagon, also support β-cell survival and have the capacity to transdifferentiate into β-cells. However, the role of α-cells in pathological conditions and their putative clinical applications remain elusive due in large part to the lack of mature α-cells. Here, we present a new technique to generate functional α-like cells. α-like cells (iAlpha cells) were generated from mouse fibroblasts by transduction of transcription factors, including Hhex, Foxa3, Gata4, Pdx1 and Pax4, which induce α-cell-specific gene expression and glucagon secretion in response to KCl and Arg stimulation. The cell functions in vivo and in vitro were evaluated. Lineage-specific and functional-related gene expression was tested by realtime PCR, insulin tolerance test (ITT), glucose tolerance test (GTT), Ki67 and glucagon immunohistochemistry analysis were done in iAlpha cells transplanted nude mice. iAlpha cells possess α-cell function in vitro and alter blood glucose levels in vivo. Transplantation of iAlpha cells into nude mice resulted in insulin resistance and increased β-cell proliferation. Taken together, we present a novel strategy to generate functional α-like cells for the purposes of disease modeling and regenerative medicine.
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참고문헌 (26)
참고문헌 신청
Ashcroft FM / 2012 / Diabetes mellitus and the β cell : the last ten years / Cell 148 : 1160 ~ 1171
Banga A / 2012 / In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts / Proc Natl Acad Sci USA 109 : 15336 ~ 15341
Chang AM / 2003 / The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2diabetic patients after a single dose / Diabetes 52 : 1786 ~ 1791
Chen S / 2009 / A small molecule that directs differentiation of human ESCs into the pancreatic lineage / Nat Chem Biol 5 : 258 ~ 265
Chung WS / 2008 / Bmp2 signaling regulates the hepatic versus pancreatic fat
Banga A / 2012 / In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts / Proc Natl Acad Sci USA 109 : 15336 ~ 15341
Chang AM / 2003 / The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2diabetic patients after a single dose / Diabetes 52 : 1786 ~ 1791
Chen S / 2009 / A small molecule that directs differentiation of human ESCs into the pancreatic lineage / Nat Chem Biol 5 : 258 ~ 265
Chung WS / 2008 / Bmp2 signaling regulates the hepatic versus pancreatic fat
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