The NLRP3 inflammasome, a multimeric protein complex, is implicated as a key driver of type 2 diabetes 5, 6. Most of these individuals have type 2 diabetes, a chronic metabolic disease characterized by insulin resistance and hyperglycemia 2.Ĭhronic inflammation is a critical facet of type 2 diabetes 3, 4. The number of people with diabetes worldwide is nearly 500 million and is projected to grow dramatically in the coming decades 1. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes. Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673 95% confidence interval, 0.638 to 0.710 P < 0.0001 95% prediction interval, 0.618 to 0.734). Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nature Communications volume 11, Article number: 4737 ( 2020)
Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development
0 kommentar(er)
