Endocrine Abstracts

NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasome-induced IL-1β production plays an important role in the pathogenesis of type 1 and type 2 diabetes mellitus (DM). Oxidative stress and inflammation interact with each other in the pathogenesis of DM. Oxidative DNA bases modified by reactive oxygen species (ROS), such as 8-OXO-2’-deoxyguanosine (8-oxoG) are repaired by 8-oxoguanine DNA glycosylase1 (OGG1). It has been previously reported that OGG1-DNA interactions facilitate NF-κB binding to DNA targets. The aim of our study was to investigate the association between serum levels of 8-oxoG, NF-κB and NLRP3 in a rat model of Streptozotocin-induced DM. We also evaluated the effect of NLRP3 activation on insulin resistance by correlating it to the triglyceride to glucose index (TyG).

Material and Methods: Sixty Wistar-Bratislava white male rats were randomly divided into three groups: negative control were injected with citrate buffer, Streptozotocin (SZT) group that received 55 mg/100 g body weight (b.w.) SZT by intraperitoneal administration and SZT+Metformin (SZT+M) (100 mg Metformin/100g b.w.). For ten days the animals received by gavage water in control and SZT groups, respectively Metformin in the SZT+M group. The serum levels of 8-oxoG and NF-κB, IL-1β, IL-18 and Gasdermin levels were determined. Additionally, we monitored the fasting glucose levels for each day during the experiment and we calculated TyG index using the formula TyG = ln [Fasting triglyceride (mg/dl) × fasting glucose (mg/dl)]/2.

Results: 8-oxoG, NF-κB, IL1B, IL-18 and Gasdemin D were significantly increased in the STZ group compared to the control group (P<0.01). In the SZT group we noticed a statistically significant positive correlation between 8-oxoG, NF-κB, IL-18, IL-1B and Gasdermin. Metformin significantly reduced IL-1B levels and in the SZT+M group we found no correlation between 8-oxoG and IL-1B. TyG index presented higher levels in the SZT group and was positively correlated to IL-1B, IL-18 and Gasdermin.

Conclusion: 8-oxoG can be used as an indicator of NF-κB/NRLP3 axis activation. Increased levels of TyG index are correlated to NLRP3 activation, indicating its role in the associated insulin resistance development.

Keywords: NLRP3 inflammasome, NF-κB, 8-oxo-2’-deoxyguanosine, Diabetes Mellitus, TyG index