Document Detail

Down-regulation of proliferation does not affect the secretory function of transformed β-cell lines regardless of their anatomical configuration.
MedLine Citation:
PMID:  21505275     Owner:  NLM     Status:  MEDLINE    
AIMS AND OBJECTIVES: Proliferation in transformed β-cell lines is high compared to primary islet cells and is accompanied by reduced insulin content and release. Our aim was to determine whether experimental reduction of proliferation restores the cells to a more authentic β-cell phenotype in terms of secretory function and to investigate the potential beneficial effect of their configuration as islet-like structures.
RESULTS: Mitosis inhibitor mitomycin c treatment neither altered the rate of proliferation nor improved the secretory responses of MIN6 monolayer cells. The proliferative rate of MIN6 cells was not affected by pseudoislet formation, but in contrast to monolayer cells, pseudoislets responded to 20 mM glucose with a 2.6-fold increase in insulin secretion. MMC reduced proliferation in MIN6 pseudoislets, but did not further improve their secretory responsiveness. Withdrawal of doxycycline resulted in complete growth-arrest in R7T1 cells, but monolayer and pseudoislet R7T1 cells were unresponsive to glucose and remained so upon growth-arrest although insulin content was increased in growth-arrested pseudoislets.
METHODS: MIN6 monolayer and pseudoislet cells were treated with MMC whereas growth-arrest was induced in R7T1 monolayer and pseudoislet cells by withdrawal of doxycycline. Proliferation rates were determined by immunocytochemical measurements of BrdU incorporation and insulin secretion was assessed by radioimmunoassay.
CONCLUSIONS: Secretory function of transformed β-cells is not influenced by experimental reduction of proliferation, but can be modulated by enhanced cell-cell contact within islet-like structures. These results have implications for future studies of islet cell redifferentiation and for the generation of islet-like material for transplantation therapy in Type 1 diabetes.
Christina Reers; Astrid C Hauge-Evans; Noel G Morgan; Abby Wilcox; Shanta J Persaud; Peter M Jones
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-05-01
Journal Detail:
Title:  Islets     Volume:  3     ISSN:  1938-2022     ISO Abbreviation:  Islets     Publication Date:    2011 May-Jun
Date Detail:
Created Date:  2011-05-12     Completed Date:  2011-09-27     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  101495366     Medline TA:  Islets     Country:  United States    
Other Details:
Languages:  eng     Pagination:  80-8     Citation Subset:  IM    
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MeSH Terms
Cell Growth Processes / drug effects,  physiology
Cell Line, Transformed
Doxycycline / pharmacology
Insulin / physiology*,  secretion
Insulin-Secreting Cells / cytology,  drug effects,  physiology*,  secretion
Mitomycin / pharmacology
Nucleic Acid Synthesis Inhibitors / pharmacology
Grant Support
G0700557/1//National Centre for the Replacement, Refinement and Reduction of Animals in Research
Reg. No./Substance:
0/Insulin; 0/Nucleic Acid Synthesis Inhibitors; 50SG953SK6/Mitomycin; N12000U13O/Doxycycline

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