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Nat Immunol. 2010 Oct;11(10):897-904. doi: 10.1038/ni.1935. Epub 2010 Sep 12.

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

Author information

1
Immunology Research Centre, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland. smasters@tcd.ie

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.

PMID:
20835230
PMCID:
PMC3103663
DOI:
10.1038/ni.1935
[Indexed for MEDLINE]
Free PMC Article

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