| First Author | Masters SL | Year | 2010 |
| Journal | Nat Immunol | Volume | 11 |
| Issue | 10 | Pages | 897-904 |
| PubMed ID | 20835230 | Mgi Jnum | J:164683 |
| Mgi Id | MGI:4834962 | Doi | 10.1038/ni.1935 |
| Citation | Masters SL, et al. (2010) Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol 11(10):897-904 |
| abstractText | Interleukin 1beta (IL-1beta) 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-1beta. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1beta production in vitro. Processing of IL-1beta 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-1beta 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. |
