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

作者：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

来源：Nature Immunology, 2010, 11(10): 897-U1501.

DOI：10.1038/ni.1935

Interleukin 1 beta (IL-1 beta) 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-1 beta. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1 beta production in vitro. Processing of IL-1 beta 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-1 beta 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.

• 出版日期2010-10