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KMID : 0620920210530040605
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Experimental & Molecular Medicine
2021 Volume.53 No. 4 p.605 ~ p.614
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Insulin-positive ductal cells do not migrate into preexisting islets during pregnancy
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Liu Qun
Jiang Yinan
Zhu Lingyan
Qian Jieqi
Wang Chaoban
Yang Tianlun
Prasadan Krishna
Gittes George K.
Xiao Xiangwei
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Abstract
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The adult pancreatic ductal system was suggested to harbor facultative beta-cell progenitors similar to the embryonic pancreas, and the appearance of insulin-positive duct cells has been used as evidence for natural duct-to-beta-cell reprogramming. Nevertheless, the phenotype and fate of these insulin-positive cells in ducts have not been determined. Here, we used a cell-tagging dye, CFDA-SE, to permanently label pancreatic duct cells through an intraductal infusion technique. Representing a time when significant increases in beta-cell mass occur, pregnancy was later induced in these CFDA-SE-treated mice to assess the phenotype and fate of the insulin-positive cells in ducts. We found that a small portion of CFDA-SE-labeled duct cells became insulin-positive, but they were not fully functional beta-cells based on the in vitro glucose response and the expression levels of key beta-cell genes. Moreover, these insulin-positive cells in ducts expressed significantly lower levels of genes associated with extracellular matrix degradation and cell migration, which may thus prevent their budding and migration into preexisting islets. A similar conclusion was reached through analysis of the Gene Expression Omnibus database for both mice and humans. Together, our data suggest that the contribution of duct cells to normal beta-cells in adult islets is minimal at best.
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KEYWORD
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Gestational diabetes, Transdifferentiation
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