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
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2014
Abstract
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..
View full abstractRelated Projects (1)
Grants
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; http://www.nhmrc.gov.au/) and Juvenile Diabetes Research Foundation (JDRF; http://www.jdrf.org/) 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 (http://www.business.vic.gov.au/grants-and-assistance/programs/medical-research-operational-infrastructure-program). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.