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

Aberrant activation of the innate immune systemin metabolic disorders such as type 2 diabeteshas been recognized to be an important mecha-nism of disease pathogenesis (1–3). Emergence of a chronic proinflammatory state driven by the activation of myeloid lineage innate immune cells, such as macro-phages and neutrophils, has been directly linked to the emergence of insulin resistance (4,5). Until recently, the identity of specific innate immune pattern recognition re-ceptors or sensors that recognize diverse metabolic “danger signals ” to initiate a proinflammatory cascade during obe-sity and diabetes was unknown. Pioneering studies from Tschopp and colleagues (6) identified that “inflamma-somes, ” the multiprotein cytosolic molecular platforms in myeloid cells, can sense damage-associated molecular pat-terns (DAMPs) and control the secretion of proinflam-matory cytokines interleukin (IL)-1b and IL-18 in metabolic stress. Structurally, inflammasomes consist of a Nod-like