Document Detail


Insulin increases H2O2-induced pancreatic beta cell death.
MedLine Citation:
PMID:  20544287     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (β) cell function, however, are unclear. In this study, we investigated the possibility that insulin may influence survival of pancreatic β cells. Studies were conducted on RINm, RINm5F and Min-6 pancreatic β-cells. Cell death was induced by treatment with H(2)O(2), and was estimated by measurements of LDH levels, viability assay (Cell-Titer Blue), propidium iodide staining and FACS analysis, and mitochondrial membrane potential (JC-1). In addition, levels of cleaved caspase-3 and caspase activity were determined. Treatment with H(2)O(2) increased cell death; this effect was increased by simultaneous treatment of cells with insulin. Insulin treatment alone caused a slight increase in cell death. Inhibition of caspase-3 reduced the effect of insulin to increase H(2)O(2)-induced cell death. Insulin increased ROS production by pancreatic β cells and increased the effect of H(2)O(2). These effects were increased by inhibition of IR signaling, indicative of an effect independent of the IR cascade. We conclude that elevated levels of insulin may act to exacerbate cell death induced by H(2)O(2) and, perhaps, other inducers of apoptosis.
Authors:
S R Sampson; E Bucris; M Horovitz-Fried; A Parnas; S Kahana; G Abitbol; M Chetboun; T Rosenzweig; C Brodie; S Frankel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  15     ISSN:  1573-675X     ISO Abbreviation:  Apoptosis     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-01     Completed Date:  2010-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1165-76     Citation Subset:  IM    
Affiliation:
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel. ssampson@013.net
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Blotting, Western
Caspases / metabolism
Cell Survival / drug effects
Cells, Cultured
Flow Cytometry
Hydrogen Peroxide / toxicity*
Insulin / metabolism*
Insulin Resistance
Insulin-Secreting Cells / drug effects*,  metabolism*
Mice
Oxidative Stress
Rats
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 11061-68-0/Insulin; 7722-84-1/Hydrogen Peroxide; EC 3.4.22.-/Caspases

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


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