Regulatory Roles of Noncanonical Inflammasomes in Diabetes Mellitus and Diabetes-Associated Complications

Inflammation is an innate immune system protecting the body from infection and injury. This process proceeds through two distinct stages: a priming phase, characterized by transcriptional activation, and a triggering phase, in which inflammasomes, cytosolic multiprotein complexes, are activated to initiate inflammatory signaling cascades. Canonical inflammasomes, the first to be identified, have been extensively implicated in the pathogenesis of diverse inflammatory disorders. In contrast, noncanonical inflammasomes have only recently been characterized, and their precise contributions to immune regulation and disease development remain incompletely defined. Diabetes mellitus (DM), simply diabetes, represents a heterogeneous group of metabolic disorders marked by chronic hyperglycemia and is associated with a broad spectrum of complications. The involvement of canonical inflammasomes in DM and its complications has been well demonstrated. More recently, however, accumulating evidence has uncovered crucial roles for noncanonical inflammasomes in the pathogenesis of DM and related complications This review comprehensively discusses current advances in understanding the regulatory functions of murine caspase-11 and human caspase-4/5 noncanonical inflammasomes in the pathogenesis of DM and diabetes-associated complications, highlighting their potential as novel therapeutic targets.