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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 9692546, 11 pages
https://doi.org/10.1155/2017/9692546
Research Article

Activation of NLRP3 Inflammasome by Advanced Glycation End Products Promotes Pancreatic Islet Damage

1Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
2Department of Endocrinology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 241001, China
3Engineering Technology Research Center of Polysaccharides Drug, Wuhu, Anhui Province 241002, China
4Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Correspondence should be addressed to Guang-Xun Meng; nc.ca.spi@gnemxg and Qing Su; moc.361@auhnixgniqus

Received 16 May 2017; Revised 5 August 2017; Accepted 29 August 2017; Published 5 November 2017

Academic Editor: Izabela Sadowska-Bartosz

Copyright © 2017 Xiang Kong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Accumulation of advanced glycation end products (AGEs) contributes to ageing and age-related diseases, especially type 2 diabetes. The NLRP3 inflammasome, as a vital component of the innate immune system, is implicated in the pathogenesis of type 2 diabetes. However, the role of the NLRP3 inflammasome in AGE-induced pancreatic islet damage remains largely unclear. Results showed that administration of AGEs (120 mg/kg for 6 weeks) in C57BL/6J mice induced an abnormal response to glucose (as measured by glucose tolerance and insulin release), pancreatic β-cell ultrastructural lesion, and cell death. These effects were associated with an excessive superoxide anion level, significant increased protein expression levels for NADPH oxidase 2 (NOX2), thioredoxin-interacting protein (TXNIP), NLRP3, and cleaved IL-1β, enhanced caspase-1 activity, and a significant increase in the levels of TXNIP–NLRP3 protein interaction. Ablation of the NLRP3 inflammasome or treatment with antioxidant N-acetyl-cysteine (NAC) clearly ameliorated these effects. In conclusion, our results reveal a possible mechanism for AGE-induced pancreatic islet damage upon NLRP3 inflammasome activation.