The NLRP3 inflammasome: a sensor for metabolic danger?

Science. 2010 Jan 15;327(5963):296-300. doi: 10.1126/science.1184003.


Interleukin-1beta (IL-1beta), reactive oxygen species (ROS), and thioredoxin-interacting protein (TXNIP) are all implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). Here we review mechanisms directing IL-1beta production and its pathogenic role in islet dysfunction during chronic hyperglycemia. In doing so, we integrate previously disparate disease-driving mechanisms for IL-1beta, ROS, and TXNIP in T2DM into one unifying model in which the NLRP3 inflammasome plays a central role. The NLRP3 inflammasome also drives IL-1beta maturation and secretion in another disease of metabolic dysregulation, gout. Thus, we propose that the NLRP3 inflammasome contributes to the pathogenesis of T2DM and gout by functioning as a sensor for metabolic stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Gout / immunology
  • Gout / metabolism
  • Humans
  • Inflammation*
  • Insulin-Secreting Cells / physiology
  • Interleukin-1beta / metabolism
  • Multiprotein Complexes / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species / metabolism
  • Stress, Physiological*


  • Carrier Proteins
  • Interleukin-1beta
  • Multiprotein Complexes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Reactive Oxygen Species
  • TXNIP protein, human