Journal
PLOS ONE
Volume 9, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0113128
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Funding
- National Health and Medical Research Council of Australia (NHMRC)
- Juvenile Diabetes Research Foundation (JDRF) [APP466658]
- NHMRC [APP1032610]
- NHMRC
- University of Melbourne Viola Edith Reid Bequest Scholarship
- Victorian Government's Operational Infrastructure Support Program
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Loss of pancreatic beta cells is a feature of type-2 diabetes. High glucose concentrations induce endoplasmic reticulum (ER) and oxidative stress-mediated apoptosis of islet cells in vitro. ER stress, oxidative stress and high glucose concentrations may also activate the NLRP3 inflammasome leading to interleukin (IL)-1 beta production and caspase-1 dependent pyroptosis. However, whether IL-1 beta or intrinsic NLRP3 inflammasome activation contributes to beta cell death is controversial. This possibility was examined in mouse islets. Exposure of islets lacking functional NLRP3 or caspase-1 to H2O2, rotenone or thapsigargin induced similar cell death as in wild-type islets. This suggests that oxidative or ER stress do not cause inflammasome-mediated cell death. Similarly, deficiency of NLRP3 inflammasome components did not provide any protection from glucose, ribose or gluco-lipotoxicity. Finally, genetic activation of NLRP3 specifically in beta cells did not increase IL-1 beta production or cell death, even in response to glucolipotoxicity. Overall, our results show that glucose-, ER stress-or oxidative stress-induced cell death in islet cells is not dependent on intrinsic activation of the NLRP3 inflammasome.
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