Nlrp3 Inflammasome Activation in Type 2 Diabetes: Is It Clinically Relevant?

Hypothetical model depicting the role of Nlrp3 inflammasome in type 2 diabetes. Metabolic stress–induced “danger signals” in type 2 diabetes such as islet amyloid polypeptide (IAPP), urate, extracellular ATP, fatty acids, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) can be sensed by Nlrp3 inflammasome. The assembly of activated Nlrp3 inflammasome in myeloid cells by protein-protein interaction between Nlrp3, Asc, and (Cardinal) with procaspase-1 causes caspase-1 cleavage into P20 and P10 enzymatically active heterodimers that causes posttranslational processing of IL-1β and IL-18. Inflammation induced by inflammasome-dependent proinflammatory cytokines may produce insulin resistance or cause death of pancreatic β-cells leading to development of diabetes. AMPK, AMP-activated protein kinase; Sirt1, sirtuin 1.