Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1ß in type 2 diabetes.
Nat Immunol
; 11(10): 897-904, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20835230
ABSTRACT
Interleukin 1ß (IL-1ß) 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-1ß. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1ß production in vitro. Processing of IL-1ß 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-1ß 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Portadoras
/
Receptores Citoplasmáticos y Nucleares
/
Diabetes Mellitus Tipo 2
/
Interleucina-1beta
/
Amiloide
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Irlanda