477-P: Inhibiting Myeloperoxidase (MPO) Prevents Onset and Reverses Established High-Fat Diet (HFD)-Induced Microvascular Insulin Resistance (IR)

HFD rapidly recruits neutrophils to insulin target tissues and induces microvascular IR. MPO is abundant in neutrophils, inhibits nitric oxide mediated vaso-relaxation, and associates with increased cardiovascular risk. AZD5904 (AstraZeneca) irreversibly inhibits MPO and is in clinical trials. MPO knockout, or chemical inhibition, improves glucose regulation in HFD-fed mice. Whether MPO affects muscle microvascular or metabolic IR in vivo is...