title: Beta-cell regeneration from vimentin+/MafB+ cells after STZ-induced extreme beta-cell ablation.
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.
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Critical Care Medicine, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Yelei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D051258:MafB Transcription Factor / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D014746:Vimentin / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D007328:Insulin; D051258:MafB Transcription Factor; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D013311:Streptozocin; D014746:Vimentin; C490405:Mafb protein, rat; C498696:Neurog3 protein, rat