OR16-05 Acute Salt-Induced Changes in Isolevuglandins in Antigen Presenting Cells Correlate with Changes in Insulin Resistance

Abstract

Disclosure: L.A. Ertuglu: None. M. Demirci: None. A. Pitzer Mutchler: None. M. Saleem: None. C.L. Laffer: None. T. Ikizler: None. A. Kirabo: None.

Study objective: Insulin resistance associates with low sodium intake and salt-sensitivity, however the underlying mechanisms remain unclear. Insulin resistance is also strongly associated with inflammation. In our previous studies, we found that sodium-induced isolevuglandin (IsoLG) formation in antigen presenting cells (APCs) leads to systemic inflammatory response resulting in salt-sensitive hypertension, and that IsoLG formation in circulating APCs changes with acute salt loading and depletion, hence is a predictor of salt sensitive hypertension. In this study, we explored whether acute salt loading and depletion would alter markers of insulin resistance and whether salt-induced changes in markers of insulin resistance relate to changes in IsoLGs formation in APCs. Methods: We measured systolic blood pressure (SBP), plasma insulin and glucose levels, and IsoLG-containing APCs (dendritic cells [DC], classical, intermediate and non-classical monocytes) by flow cytometry and a specific antibody, in 20 hypertensive subjects who were off of anti-hypertensive therapy for 2 weeks, at baseline and after in-patient 24 hr salt loading (HiNa, 460 mmol Na⁺) and salt depletion (LoNa, 10 mmol Na⁺ and furosemide 40 mg x 3). Salt sensitivity was assessed by salt sensitivity index, which was calculated as ΔSBP (HiNa minus LoNa). HOMA-IR was calculated with the following formula: [fasting plasma glucose level (mg/dL) × fasting serum insulin level (μU/mL)]/405. Results: Mean (±SEM) age was 54±1.8, with 12 females and mean BMI was 31.2± 1.4 kg/m². HOMA IR was 4.5±1.0; 5.9 ± 1.13 and 10.91 ± 2.65 at baseline, HiNa and LoNa, respectively. Baseline HOMA IR positively correlated with salt sensitivity (r= 0.50, p=0.02). HOMA IR was significantly higher after LoNa compared to HiNa (p<0.001). Changes in HOMA IR from HiNa to LoNa negatively correlated with changes in percentages of IsoLG-containing APCs (r=-0.74, p<0.001, r=-0.76, p<0.001, r=-0.71, p=0.001, r=-0.79, p<0.001 for DC, classical, intermediate and non-classical monocytes, respectively). Conclusion: Insulin resistance increases with increasing salt sensitivity. Markers of insulin resistance increase in response to acute decrease in salt intake within 24 hours, and this change significantly correlates with changes in IsoLG formation in APCs, suggesting that oxidative stress in APCs may be implicated in salt-sensitive changes in glucose metabolism. The precise mechanisms by which plasma insulin/glucose relate with IsoLG formation in APCs remains to be elucidated. Funding: supported by NIH R01HL144941

Presentation: Sunday, July 13, 2025