REVIEW The NLRP3 Inflammasome: A Sensor for Metabolic Danger?

Interleukin-1b (IL-1b), 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-1b production and its pathogenic role in islet dysfunction during chronic hyperglycemia. In doing so, we integrate previously disparate disease-driving mechanisms for IL-1b, ROS, and TXNIP in T2DM into one unifying model in which the NLRP3 inflammasome plays a central role. The NLRP3 inflammasome also drives IL-1b 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. Type 2 diabetes mellitus (T2DM) mani-fests when pancreatic b cells fail to com-pensate for chronic elevated blood glucose (hyperglycemia) that occurs when glucose uptake in the periphery becomes dysregulated during insulin resistance. Insulin is secreted by pancre-atic b cells upon hyperglycemia and regulates glucose utilization within the body. In healthy individuals, postfeeding hyperglycemia is tran