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Sci Rep. 2015 Jul 1;5:11703. doi: 10.1038/srep11703.

Beta-cell regeneration from vimentin+/MafB+ cells after STZ-induced extreme beta-cell ablation.

Author information

1
1] Department of Endocrinology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China [2] Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
2
Department of Critical Care Medicine, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
3
1] Department of Endocrinology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China [2] Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China [3] Department of Endocrinology, Chinese PLA 309 Hospital, 17 Heishanhu Road, Beijing 100091, China.
4
Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
5
Department of Endocrinology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.

Abstract

Loss of functional beta-cells is fundamental in both type 1 and type 2 diabetes. In situ beta-cell regeneration therefore has garnered great interest as an approach to diabetes therapy. Here, after elimination of pre-existing beta cells by a single high-dose of streptozotocin (STZ), we demonstrated that a considerable amount of beta-like-cells was generated within 48 hrs. But the newly formed insulin producing cells failed to respond to glucose challenge at this time and diminished afterwards. Insulin treatment to normalize the glucose level protected the neogenic beta-like cells and the islet function was also gradually matured. Strikingly, intermediate cells lacking epithelial marker E-cadherin but expressing mesenchymal cell-specific marker vimentin appeared within 16 hrs following STZ exposure, which served as the major source of insulin-producing cells observed at 24 hrs. Moreover, these intermediate cells strongly expressed alpha-cell-specific marker MafB. In summary, the data presented here identified a novel intermediate cell type as beta-cell progenitors, showing mesenchymal cell feature as well as alpha-cell marker MafB. Our results might have important implications for efforts to stimulate beta-cell regeneration.

PMID:
26129776
PMCID:
PMC4486952
DOI:
10.1038/srep11703
[Indexed for MEDLINE]
Free PMC Article

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