NLRP3 Inhibitor Tranilast Attenuates Gestational Diabetes Mellitus in a Genetic Mouse Model

BACKGROUND AND OBJECTIVE: This study was designed to explore the protective effects of a clinically available NLR family Pyrin domain-containing receptor 3 (NLRP3) inhibitor, tranilast, in gestational diabetes mellitus (GDM) mice. METHODS: We used pregnant C57BL/KsJdb/+ (db/+) female mice as GDM mice, then orally administered 20 mg/kg of tranilast or metformin daily for 2 weeks. A glucose tolerance test and an insulin resistance test were used to evaluate the severity of diabetes in tranilast/metformin-treated GDM mice. After delivery, newborn mice were counted and weighed to measure their protective role on the reproductive outcome of GDM mice. Next, we determined the expression of NLRP3 and proinflammatory cytokines in the visceral adipose tissue and placenta of GDM mice using western blot and quantitative real-time-polymerase chain reaction. Furthermore, we determined the proinflammatory cytokines in the serum using an enzyme-linked immunosorbent assay. RESULTS: Tranilast significantly ameliorated GDM symptoms, including maternal body weight, hyperglycemia, insulin insufficiency, glucose intolerance and insulin resistance, enlarged litter size, and reduced litter body weight. Additionally, tranilast remarkably reduced the elevated expression of NLRP3 and proinflammatory cytokines. CONCLUSIONS: Our data clarified the protective role of the NLRP3 inhibitor, tranilast, on GDM by inhibiting the activation of the NLRP3 inflammasome as well as inflammatory responses. The findings mean tranilast might serve as a therapeutic drug to treat GDM.