Details

Autor(en) / Beteiligte

• 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
• Nuñez, Gabriel
• Yodoi, Junji
• Kahn, Steven E
• Lavelle, Ed C
• O'Neill, Luke A J

Titel

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

Ist Teil von

• Nature immunology, 2010-10, Vol.11 (10), p.897-904

Ort / Verlag

United States

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.