Antigen-Presenting Cell Isolevuglandins Link Salt Sensitivity of Blood Pressure to Insulin Resistance.

Abstract

Insulin resistance has been associated with salt sensitivity and low sodium intake; however, the mechanisms remain elusive. Our previous studies showed that sodium-induced isolevuglandin (IsoLG) formation in antigen-presenting cells (APCs) leads to systemic inflammation and that salt-sensitive hypertension and IsoLG formation in APCs are affected by acute alterations in salt intake in salt-sensitive but not salt-resistant people. In this clinical study, we investigated how acute salt loading and depletion change insulin resistance markers and whether these changes are linked with changes in IsoLGs in APCs. A total of 20 participants with hypertension underwent an inpatient protocol of salt loading and depletion for assessment of salt sensitivity. Plasma glucose and insulin levels were measured after 24 hours of salt loading and depletion and insulin resistance was measured by the homeostasis model assessment index (HOMA-IR). IsoLG-adduct accumulation in APCs (dendritic cells, classical, intermediate and nonclassical monocytes) was assessed by flow cytometry. Baseline insulin resistance correlated with higher salt sensitivity. Insulin resistance significantly increased from salt loading to salt depletion. Salt depletion induced changes in IsoLG + APCs significantly correlated with changes in HOMA-IR. This correlation was significant only in participants who were insulin resistant at baseline. Within 24 hours of acute salt depletion, markers of insulin resistance exhibit a significant increase, which strongly correlates with change in IsoLG formation in APCs. This finding implies that oxidative stress in APCs may be implicated in the salt-sensitive modulation of glucose metabolism.