From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1538-43. doi: 10.1161/ATVBAHA.115.305447. Epub 2015 Apr 23.
The insulinotropic gut-derived hormone glucagon-like peptide-1 (GLP-1) increases capillary perfusion via a nitric oxide-dependent mechanism in rodents. This improves skeletal muscle glucose use and cardiac function. In humans, the effect of clinically used GLP-1 receptor agonists (GLP-1RAs) on capillary density is unknown. We aimed to assess the effects of the GLP-1RA exenatide on capillary density as well as the involvement of nitric oxide in humans.
We included 10 healthy overweight men (age, 20-27 years; body mass index, 26-31 kg/m(2)). Measurements were performed during intravenous infusion of placebo (saline 0.9%), exenatide, and a combination of exenatide and the nonselective nitric oxide-synthase inhibitor L-N(G)-monomethyl arginine. Capillary videomicroscopy was performed, and baseline and postocclusive (peak) capillary densities were counted. Compared with placebo, exenatide increased baseline and peak capillary density by 20.1% and 8.3%, respectively (both P=0.016). Concomitant L-N(G)-monomethyl arginine infusion did not alter the effects of exenatide. Vasomotion was assessed using laser Doppler fluxmetry. Exenatide nonsignificantly reduced the neurogenic domain of vasomotion measurements (R=-5.6%; P=0.092), which was strongly and inversely associated with capillary perfusion (R=-0.928; P=0.036). Glucose levels were reduced during exenatide infusion, whereas levels of insulin were unchanged.
Acute exenatide infusion increases capillary perfusion via nitric oxide-independent pathways in healthy overweight men, suggesting direct actions of this GLP-1RA on microvascular perfusion or interaction with vasoactive factors.
肠源胰岛素促分泌激素胰高血糖素样肽-1（GLP-1）通过一氧化氮依赖机制增加毛细血管灌注，从而改善骨骼肌葡萄糖利用和心脏功能。在人类中，临床应用的 GLP-1 受体激动剂（GLP-1RAs）对毛细血管密度的影响尚不清楚。我们旨在评估 GLP-1RA 艾塞那肽对毛细血管密度的影响，以及一氧化氮在其中的作用。
我们纳入了 10 名健康超重男性（年龄 20-27 岁；体重指数 26-31kg/m2）。在静脉输注安慰剂（生理盐水 0.9%）、艾塞那肽和艾塞那肽与非选择性一氧化氮合酶抑制剂 L-N（G）-单甲基精氨酸联合输注期间进行了测量。进行了毛细血管视频显微镜检查，并计数基线和闭塞后（峰值）毛细血管密度。与安慰剂相比，艾塞那肽分别使基线和峰值毛细血管密度增加了 20.1%和 8.3%（均 P=0.016）。同时输注 L-N（G）-单甲基精氨酸并未改变艾塞那肽的作用。使用激光多普勒通量测量评估血管舒缩运动。艾塞那肽对血管舒缩运动测量的神经源性域的作用无显著影响（R=-5.6%；P=0.092），而与毛细血管灌注呈强烈负相关（R=-0.928；P=0.036）。艾塞那肽输注期间血糖水平降低，而胰岛素水平不变。
急性艾塞那肽输注通过一氧化氮非依赖性途径增加健康超重男性的毛细血管灌注，提示这种 GLP-1RA 对微血管灌注具有直接作用，或与血管活性因子相互作用。
