Document Detail


Pancreatic β-cell neogenesis by direct conversion from mature α-cells.
MedLine Citation:
PMID:  20653050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Because type 1 and type 2 diabetes are characterized by loss of β-cells, β-cell regeneration has garnered great interest as an approach to diabetes therapy. Here, we developed a new model of β-cell regeneration, combining pancreatic duct ligation (PDL) with elimination of pre-existing β-cells with alloxan. In this model, in which virtually all β-cells observed are neogenic, large numbers of β-cells were generated within 2 weeks. Strikingly, the neogenic β-cells arose primarily from α-cells. α-cell proliferation was prominent following PDL plus alloxan, providing a large pool of precursors, but we found that β-cells could form from α-cells by direct conversion with or without intervening cell division. Thus, classical asymmetric division was not a required feature of the process of α- to β-cell conversion. Intermediate cells coexpressing α-cell- and β-cell-specific markers appeared within the first week following PDL plus alloxan, declining gradually in number by 2 weeks as β-cells with a mature phenotype, as defined by lack of glucagon and expression of MafA, became predominant. In summary, these data revealed a novel function of α-cells as β-cell progenitors. The high efficiency and rapidity of this process make it attractive for performing the studies required to gain the mechanistic understanding of the process of α- to β-cell conversion that will be required for eventual clinical translation as a therapy for diabetes.
Authors:
Cheng-Ho Chung; Ergeng Hao; Ron Piran; Ehud Keinan; Fred Levine
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  28     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-30     Completed Date:  2010-11-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1630-8     Citation Subset:  IM    
Affiliation:
Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Biological Markers / metabolism
Cell Proliferation*
Cell Transdifferentiation*
Diabetes Mellitus, Experimental / metabolism,  pathology*
Glucagon / metabolism
Glucagon-Secreting Cells / metabolism,  pathology*
Insulin / metabolism
Insulin-Secreting Cells / metabolism,  pathology*
Lectins, C-Type / metabolism
Ligation
MafB Transcription Factor / metabolism
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Oncogene Proteins / metabolism
Pancreatic Ducts / surgery
Phenotype
Regeneration*
Time Factors
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Klrg1 protein, rat; 0/Lectins, C-Type; 0/MafB Transcription Factor; 0/Mafb protein, rat; 0/Membrane Glycoproteins; 0/Oncogene Proteins; 11061-68-0/Insulin; 9007-92-5/Glucagon

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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