Document Detail

Iterative exposure of clonal BRIN-BD11 cells to ninhydrin enables selection of robust toxin-resistant cells but with decreased gene expression of insulin secretory function.
MedLine Citation:
PMID:  18362844     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Prevention of pancreatic beta-cell destruction combined with preservation of insulin secretory function is an important goal for cell-based diabetes therapy. This study describes the generation and characteristics of toxin-resistant beta-cells. METHODS: By using iterative exposures to ninhydrin, a new class of robust ninhydrin-tolerant insulin-secreting BRIN-BD11 ninhydrin-tolerant (BRINnt) cells was generated. Low- and high-passage BRINnt cells were used to evaluate beta-cell function and tolerance against toxins in comparison with native BRIN-BD11 cells. Differences in viability, gene expression, insulin secretory function, antioxidant enzyme activity, DNA damage, and DNA repair efficiency were compared. RESULTS: BRIN-BD11 ninhydrin-tolerant cells exhibited resistance toward ninhydrin and hydrogen peroxide but not streptozotocin (STZ). Both total superoxide dismutase (SOD) and catalase enzyme activities of BRINnt cells were significantly enhanced, and ninhydrin-induced DNA damage was decreased. BRIN-BD11 ninhydrin-tolerant cells also exhibited enhanced DNA repair efficiency. However, this was accompanied by loss of secretagogue-induced insulin release, decreased cellular insulin content, and deficits in insulin and glucose transporter 2 gene expression. Prolonged culture of BRINnt cells in the absence of ninhydrin reversed the degenerated function of BRINnt cells but restored ninhydrin susceptibility. CONCLUSIONS: These data illustrate dissociation between beta-cell toxin resistance and secretory function, indicating difficulties in generation of robust and well-functioning cells using this approach.
Hui-Kang Liu; Jane T McCluskey; Neville H McClenghan; Peter R Flatt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pancreas     Volume:  36     ISSN:  1536-4828     ISO Abbreviation:  Pancreas     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-25     Completed Date:  2008-04-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8608542     Medline TA:  Pancreas     Country:  United States    
Other Details:
Languages:  eng     Pagination:  294-301     Citation Subset:  IM    
School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK.
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MeSH Terms
Antioxidants / metabolism
Catalase / metabolism
Clone Cells
DNA Damage
DNA Repair / drug effects
Drug Resistance
Gene Expression / drug effects
Glucose Transporter Type 2 / genetics
Hydrogen Peroxide / toxicity
Insulin / metabolism,  secretion*
Insulin-Secreting Cells / cytology,  drug effects*,  physiology*,  secretion
Ninhydrin / pharmacology*
Streptozocin / toxicity
Superoxide Dismutase / metabolism
Reg. No./Substance:
0/Antioxidants; 0/Glucose Transporter Type 2; 0/Slc2a2 protein, rat; 11061-68-0/Insulin; 18883-66-4/Streptozocin; 485-47-2/Ninhydrin; 7722-84-1/Hydrogen Peroxide; EC; EC Dismutase

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