PURPOSE To elucidate the impact of elevated free fatty acids (FFAs) on insulin action across the arterial tree and define the relationship among insulin actions in the different arterial segments. METHODS This randomized crossover study assigned healthy lean adults to two separate admissions with euglycemic insulin clamp superimposed for the final 120-mins of 5-hr lipid or matched-volume saline infusion. Vascular measures including peripheral and central arterial blood pressure, brachial artery flow-mediated dilation (FMD), carotid femoral pulse wave velocity (cfPWV), augmentation index (AIx), pulse wave separation analysis, subendocardial viability ratio (SEVR), and skeletal and cardiac muscle microvascular perfusion were determined before and after insulin clamp. Insulin-mediated whole body glucose disposal was calculated. RESULTS Insulin enhanced FMD, AIx, reflection magnitude, and cardiac and skeletal muscle microvascular perfusion. Elevation of plasma FFA concentrations to the levels seen in the post-absorptive state in people with insulin resistance suppressed SEVR, blunted insulin-induced increases in FMD and cardiac and skeletal muscle microvascular blood volume, and lowered insulin's ability to reduce AIx and reflection magnitude. In multivariate regression, insulin-mediated muscle microvascular perfusion was independently associated with insulin-mediated FMD and cfPWV. MAIN CONCLUSIONS Clinically relevant elevation of plasma FFA concentrations induces pan-arterial insulin resistance, the vascular insulin resistance outcomes are interconnected, and insulin-mediated muscle microvascular perfusion associates with cardiovascular disease predictors. Our data provide biologic plausibility whereby a causative relationship between FFAs and cardiovascular disease could exist, and suggest that further attention to interventions which block FFA-mediated vascular insulin resistance may be warranted.

中文翻译：

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游离脂肪酸对整个动脉树血管胰岛素反应的影响：随机交叉研究。

目的 阐明游离脂肪酸 (FFA) 升高对整个动脉树胰岛素作用的影响，并确定不同动脉节段胰岛素作用之间的关系。方法 这项随机交叉研究将健康瘦成人分入两次单独入院，并在最后 120 分钟叠加正常血糖的胰岛素钳夹或 5 小时脂质或匹配体积的盐水输注。血管测量包括外周和中心动脉血压、肱动脉血流介导的扩张 (FMD)、颈动脉脉搏波速度 (cfPWV)、增强指数 (AIx)、脉搏波分离分析、心内膜下活力比 (SEVR) 以及骨骼和测定胰岛素钳夹前后心肌微血管灌注情况。计算了胰岛素介导的全身葡萄糖处理。结果 胰岛素增强 FMD、AIx、反射幅度以及心脏和骨骼肌微血管灌注。将血浆 FFA 浓度升高至胰岛素抵抗患者吸收后状态的水平，可抑制 SEVR，减弱胰岛素诱导的 FMD 以及心肌和骨骼肌微血管血容量的增加，并降低胰岛素降低 AIx 和反射强度的能力。在多变量回归中，胰岛素介导的肌肉微血管灌注与胰岛素介导的 FMD 和 cfPWV 独立相关。主要结论 临床相关的血浆 FFA 浓度升高会诱发全动脉胰岛素抵抗，血管胰岛素抵抗结果是相互关联的，胰岛素介导的肌肉微血管灌注与心血管疾病预测因子相关。我们的数据提供了生物学上的合理性，即 FFA 与心血管疾病之间可能存在因果关系，并表明可能需要进一步关注阻断 FFA 介导的血管胰岛素抵抗的干预措施。