Document Detail

Streptozotocin-resistant BRIN-BD11 cells possess wide spectrum of toxin tolerance and enhanced insulin-secretory capacity.
MedLine Citation:
PMID:  17992598     Owner:  NLM     Status:  MEDLINE    
Since streptozotocin (STZ) exhibits beta-cell toxicity, mediated through diverse mechanisms, multiple toxin resistance can be expected in insulin-secretory cells rendered STZ-resistant. RINm5F, but not all cell lines surviving STZ treatment, possess higher insulin content than native parental cells and additional tolerance against alloxan. To understand the impact of STZ tolerant cell selection on toxin resistance and insulin-secretory function, STZ-resistant BRIN-BD11 cells were generated by iterative acute exposure to 20 mM STZ. These cells, denoted BRINst cells, exhibited resistance to toxic challenges from STZ, H(2)O(2), and ninhydrin. Insulin content and both glucose and arginine-stimulated insulin secretion were significantly enhanced in BRINst cells. The toxin-resistance of BRINst cells was gradually lost during continuous cultivation without STZ challenge. However, enhanced insulin secretory capacity at high passage in BRINst cells persisted. Although total SOD activity was decreased, catalase activity was increased and appeared to be important for the ninhydrin and STZ resistance of BRINst cells. This was associated with reductions of both STZ- and ninhydrin-induced DNA damage, although DNA repair was abolished. Further characterization of cells exhibiting multiple toxin tolerance and an enhanced insulin secretory function could provide useful lessons for understanding of beta-cell survival.
Hui-Kang Liu; Jane T McCluskey; Neville H McClenghan; Peter R Flatt
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Publication Detail:
Type:  Journal Article     Date:  2007-09-29
Journal Detail:
Title:  Endocrine     Volume:  32     ISSN:  1355-008X     ISO Abbreviation:  Endocrine     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-11-09     Completed Date:  2008-03-27     Revised Date:  2010-06-24    
Medline Journal Info:
Nlm Unique ID:  9434444     Medline TA:  Endocrine     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20-9     Citation Subset:  IM    
School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK.
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MeSH Terms
Antibiotics, Antineoplastic / pharmacology
Antioxidants / metabolism*
Cell Culture Techniques
DNA Damage
DNA Repair / physiology*
Drug Resistance, Multiple / physiology*
Glucose / metabolism
Hydrogen Peroxide / pharmacology
Insulin / biosynthesis,  secretion
Insulin-Secreting Cells / metabolism*,  secretion
Ninhydrin / pharmacology
Oxidants / pharmacology
Radiation-Sensitizing Agents / pharmacology
Signal Transduction / physiology*
Streptozocin / pharmacology
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antioxidants; 0/Oxidants; 0/Radiation-Sensitizing Agents; 11061-68-0/Insulin; 18883-66-4/Streptozocin; 485-47-2/Ninhydrin; 50-99-7/Glucose; 7722-84-1/Hydrogen Peroxide

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