biostudies-literatureZhao HNational Natural Science Foundation of China931087https://www.ebi.ac.uk/biostudies/studies/S-EPMC9513153biostudies-literatureUnknown13<h4>Aim</h4>Numerous reports have demonstrated the key importance of macrophage-elicited metabolic inflammation in insulin resistance (IR). Our previous studies confirmed that hyperuricemia or high uric acid (HUA) treatment induced an IR state in several peripheral tissues to promote the development of type 2 diabetes mellitus (T2DM). However, the effect of HUA on glucose uptake and the insulin sensitivity of macrophages and its mechanism is unclear.<h4>Methods</h4>To assess systemic IR, we generated hyperuricemic mice by urate oxidase knockout (UOX-KO). Then, glucose/insulin tolerance, the tissue uptake of 18F-fluorodeoxyglucose, body composition, and energy balance were assessed. Glucose uptake of circulating infiltrated macrophages in the liver was evaluated by glucose transporter type Frontiers in immunologyHyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathway <i>via</i> IRS2-proteasome degradation.PMC951315381570772He FYu LXi YYamamoto TXu CYan YChen BLiu WWang MWang QXieLu JKoyama HYu WWang WZhang CZhao HCheng JfalseHyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathway <i>via</i> IRS2-proteasome degradation.<h4>Aim</h4>Numerous reports have demonstrated the key importance of macrophage-elicited metabolic inflammation in insulin resistance (IR). Our previous studies confirmed that hyperuricemia or high uric acid (HUA) treatment induced an IR state in several peripheral tissues to promote the development of type 2 diabetes mellitus (T2DM). However, the effect of HUA on glucose uptake and the insulin sensitivity of macrophages and its mechanism is unclear.<h4>Methods</h4>To assess systemic IR, we generated hyperuricemic mice by urate oxidase knockout (UOX-KO). Then, glucose/insulin tolerance, the tissue uptake of 18F-fluorodeoxyglucose, body composition, and energy balance were assessed. Glucose uptake of circulating infiltrated macrophages in the liver was evaluated by glucose transporter type 2022-01-01T00:00:00Z20222026-05-27T23:38:04.246Z2024-11-19T17:00:38.308ZS-EPMC95131533617703710.3389/fimmu.2022.931087