The NLRP3 inflammasome: a sensor for metabolic danger?
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.
Schroder
Kate
K
Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
Zhou
Rongbin
R
Tschopp
Jurg
J
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006073:Gout / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D050417:Insulin-Secreting Cells / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological
D002352:Carrier Proteins; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; C486715:TXNIP protein, human