Free Fatty Acids Induce Insulin Resistance in Both Cardiac and Skeletal Muscle Microvasculature in Humans
Free Fatty Acids Induce Insulin Resistance in Both Cardiac and Skeletal Muscle Microvasculature in Humans
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DOI：
10.1210/jc.2010-1174
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发表时间：
2011-02-01
影响因子：
5.8
通讯作者：
Liu, Zhenqi
中科院分区：
文献类型：
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作者：
Liu, Jia;Jahn, Linda A.;Liu, Zhenqi
背景：胰岛素在心肌和骨骼肌中募集微血管，增加内皮交换表面积。糖尿病患者血浆游离脂肪酸（FFA）浓度升高，这会损害胰岛素介导的骨骼肌微血管募集。目的：本研究的目的是检查FFA升高是否同样会导致心肌微血管胰岛素抵抗。设置：本研究在弗吉尼亚大学的综合临床研究中心进行。方法：22名健康的年轻人在禁食一夜后随机接受了两次研究。每例受试者接受5小时全身输注生理盐水或Intralidid/肝素，输注速率为1 mU/min。kg正葡萄糖胰岛素钳夹叠加最后2 h。结果：胰岛素使心肌和骨骼肌的微血管血容量（MBV）和微血管血流量（MBF）显著增加（P均< 0.0001），骨骼肌的MBV和MBF显著增加（P分别为0.008和< 0.03）。微血管流速略有增加，但在骨骼（P = 0.04），但不是在心肌显着。脂质输注降低了胰岛素刺激的全身葡萄糖处置，并消除了胰岛素介导的心肌和骨骼肌MBV和MBF增加。全身胰岛素敏感性可预测骨骼肌而非心肌对胰岛素的微血管反应。胰岛素甚至降低骨骼肌MBV在脂质输注过程中的受试者谁是中度敏感的胰岛素metabolically.Conclusions：总之，高血浆浓度的游离脂肪酸导致胰岛素抵抗的心脏以及骨骼肌微血管在健康的人。这可能有助于糖尿病心脏并发症与代谢性胰岛素抵抗的相关性。（临床内分泌代谢杂志96：438-446，2011）
Context: Insulin recruits microvasculature in both cardiac and skeletal muscle, which increases the endothelial exchange surface area. Plasma concentrations of free fatty acids (FFAs) are elevated in patients with diabetes, which impairs insulin-mediated skeletal muscle microvascular recruitment.Objective: The objective of the study was to examine whether elevated FFAs likewise cause insulin resistance in cardiac muscle microvasculature.Setting: The study was conducted at the General Clinical Research Center at the University of Virginia.Methods: Twenty-two healthy, young adults were studied twice in random order after an overnight fast. Each subject received a 5-h systemic infusion of either saline or Intralipid/heparin with a 1 mU/min . kg euglycemic insulin clamp superimposed for the last 2 h. Cardiac and forearm skeletal muscle microvascular blood volume (MBV) and flow velocity were measured and microvascular blood flow (MBF) calculated before and at the end of the insulin infusion.Results: Insulin significantly increased MBV and MBF in both cardiac (P < 0.0001 for both) and skeletal (P = 0.008 and < 0.03, respectively) muscle. Microvascular flow velocity increased slightly but significantly in the skeletal (P = 0.04) but not in cardiac muscle. Lipid infusion lowered insulin-stimulated whole-body glucose disposal and abolished insulin-mediated increases in MBV and MBF in both cardiac and skeletal muscle. Whole-body insulin sensitivity predicted skeletal but not cardiac muscle microvascular responses to insulin. Insulin even decreased skeletal muscle MBV during lipid infusion in subjects who were moderately sensitive to insulin metabolically.Conclusions: In conclusion, high plasma concentrations of FFAs cause insulin resistance in cardiac as well as skeletal muscle microvasculature in healthy humans. This may contribute to the association of cardiac complications with metabolic insulin resistance in diabetes. (J Clin Endocrinol Metab 96: 438-446, 2011)