Insulin-positive ductal cells do not migrate into preexisting islets during pregnancy

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 insul...

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Veröffentlicht in:Experimental & molecular medicine 2021, 53(0), , pp.1-10
Hauptverfasser: Liu, Qun, Jiang, Yinan, Zhu, Lingyan, Qian, Jieqi, Wang, Chaoban, Yang, Tianlun, Prasadan, Krishna, Gittes, George K., Xiao, Xiangwei
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Sprache:eng
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Zusammenfassung: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. Diabetes: Tracing cells that might transform to produce insulin The tantalizing possibility that the adult pancreas harbors cells that could transform into insulin-producing cells called beta cells appears unlikely. Past research indicated that cells lining the ducts of the pancreas had the potential to differentiate into beta cells, which produce insulin to control blood sugar. Using a mouse model, Xiangwei Xiao at the University of Pittsburgh School of Medicine, USA, and Lingyan Zhu at the First Affiliated Hospital of NanChang University, China, tagged pancreatic duct cells with a special dye, then traced them to see if they became functioning beta cells. Although the cells did produce trace amounts of insulin, they did not produce insulin in response to glucose, nor express all the genes expressed by a mature beta cell. These results enhance our understanding of beta cell development and insulin production.
ISSN:1226-3613
2092-6413
DOI:10.1038/s12276-021-00593-z