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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Masters SL,Dunne A,Subramanian SL,Hull RL,Tannahill GM,Sharp FA,Becker C,Franchi L,Yoshihara E,Chen Z,Mullooly N,Mielke LA,Harris J,Coll RC,Mills KH,Mok KH,Newsholme P,Nuñez G,Yodoi J,Kahn SE,Lavelle EC,O'Neill

doi

10.1038/ni.1935

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

897-904

issue

10

eissn

1529-2908

issn

1529-2916

pii

ni.1935

journal_volume

11

pub_type

杂志文章

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