More importantly, based on the beneficial effects of blocking the activation of the NLRP3 inflammasome, we provided a potential therapeutic target for clinical comorbidity and a new strategy for management of both diabetes and depression.
At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes.
NLRP3 inflammasome activation and vascular endothelial injury were significantly increased in APN-KO mice compared with WT mice in diabetes and MCC950 decreased diabetic vascular endothelial dysfunction to comparable levels in APN-KO mice and WT mice.
NLRP3- and IL-1R-deficient mice, but not ASC-deficient mice, showed reduced incidence of diabetes, less insulitis, lower hyperglycemia, and normal insulin levels compared to wild-type (WT) diabetic mice.
NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after.
Thioredoxin-interacting protein (TXNIP), a regulator of cellular oxidative stress, has been associated with activation of NOD-like receptor 3 (NLRP3) inflammasome, inflammation and lipid metabolism, suggesting it has a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in diabetes.
Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue inflammation in diseases including gout and those that previously have not been considered inflammatory in nature such as diabetes, fibrosing lung disease and possibly coronary artery disease.