Journal article

Activation of the NLRP3 Inflammasome Complex is Not Required for Stress-Induced Death of Pancreatic Islets

Jibran A Wali, Esteban N Gurzov, Stacey Fynch, Lorraine Elkerbout, Thomas W Kay, Seth L Masters, Helen E Thomas



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)-1β production and caspase-1 dependent pyroptosis. However, whether IL-1β 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 oxidativ..

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Awarded by Juvenile Diabetes Research Foundation (JDRF)

Awarded by NHMRC

Funding Acknowledgements

This study was supported by a National Health and Medical Research Council of Australia (NHMRC; and Juvenile Diabetes Research Foundation (JDRF; joint special program grant in type 1 diabetes (APP466658), an NHMRC project grant (APP1032610), fellowships from the NHMRC (HET and SLM) and a University of Melbourne Viola Edith Reid Bequest Scholarship (JAW). This study was supported in part by the Victorian Government's Operational Infrastructure Support Program ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.