Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β 2 in type 2 diabetes

Masters, Seth L., Dunne, Aisling, Subramanian, Shoba L., Hull, Rebecca L., Tannahill, Gillian M., Sharp, Fiona A., Becker, Christine, Franchi, Luigi, Yoshihara, Eiji, Chen, Zhe, Mullooly, Niamh, Mielke, Lisa A., Harris, James, Coll, Rebecca C., Mills, Kingston H. G., Mok, K. Hun, Newsholme, Philip, Nunez, Gabriel, Yodoi, Junji, Kahn, Steven E., Lavelle, Ed C. and O'Neill, Luke A. J. (2010) Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β 2 in type 2 diabetes. Nature Immunology, 11 10: 897-904. doi:10.1038/ni.1935


Author Masters, Seth L.
Dunne, Aisling
Subramanian, Shoba L.
Hull, Rebecca L.
Tannahill, Gillian M.
Sharp, Fiona A.
Becker, Christine
Franchi, Luigi
Yoshihara, Eiji
Chen, Zhe
Mullooly, Niamh
Mielke, Lisa A.
Harris, James
Coll, Rebecca C.
Mills, Kingston H. G.
Mok, K. Hun
Newsholme, Philip
Nunez, Gabriel
Yodoi, Junji
Kahn, Steven E.
Lavelle, Ed C.
O'Neill, Luke A. J.
Title Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β 2 in type 2 diabetes
Journal name Nature Immunology   Check publisher's open access policy
ISSN 1529-2908
1529-2916
Publication date 2010-11
Sub-type Article (original research)
DOI 10.1038/ni.1935
Open Access Status
Volume 11
Issue 10
Start page 897
End page 904
Total pages 8
Place of publication New York, United States
Publisher Nature
Language eng
Formatted abstract
Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1β production in vitro. Processing of IL-1β initiated by IAPP first required priming, a process that involved glucose metabolism and was facilitated by minimally oxidized low-density lipoprotein. Finally, mice transgenic for human IAPP had more IL-1β in pancreatic islets, which localized together with amyloid and macrophages. Our findings identify previously unknown mechanisms in the pathogenesis of type 2 diabetes and treatment of pathology caused by IAPP.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 444 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 468 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 08 Aug 2014, 18:55:04 EST by System User on behalf of Institute for Molecular Bioscience