*Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
†Division of Cardiovascular Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
Clin Sci (Lond). 2014 Aug;127(3):163-70. doi: 10.1042/CS20130708.
Muscle microvascular surface area determines substrate and hormonal exchanges between plasma and muscle interstitium. GLP-1 (glucagon-like peptide-1) regulates glucose-dependent insulin secretion and has numerous extrapancreatic effects, including a salutary vascular action. To examine whether GLP-1 recruits skeletal and cardiac muscle microvasculature in healthy humans, 26 overnight-fasted healthy adults received a systemic infusion of GLP-1 (1.2 pmol/kg of body mass per min) for 150 min. Skeletal and cardiac muscle MBV (microvascular blood volume), MFV (microvascular flow velocity) and MBF (microvascular blood flow) were determined at baseline and after 30 and 150 min. Brachial artery diameter and mean flow velocity were measured and total blood flow was calculated before and at the end of the GLP-1 infusion. GLP-1 infusion raised plasma GLP-1 concentrations to the postprandial levels and suppressed plasma glucagon concentrations with a transient increase in plasma insulin concentrations. Skeletal and cardiac muscle MBV and MBF increased significantly at both 30 and 150 min (P<0.05). MFV did not change in skeletal muscle, but decreased slightly in cardiac muscle. GLP-1 infusion significantly increased brachial artery diameter (P<0.005) and flow velocity (P=0.05) at 150 min, resulting in a significant increase in total brachial artery blood flow (P<0.005). We conclude that acute GLP-1 infusion significantly recruits skeletal and cardiac muscle microvasculature in addition to relaxing the conduit artery in healthy humans. This could contribute to increased tissue oxygen, nutrient and insulin delivery and exchange and therefore better prandial glycaemic control and tissue function in humans.
肌肉微血管表面积决定了血浆与肌肉间质之间的底物和激素交换。GLP-1(胰高血糖素样肽-1)调节葡萄糖依赖性胰岛素分泌,并具有许多胰外作用,包括有益的血管作用。为了研究 GLP-1 是否在健康人中募集骨骼肌和心肌微血管,26 名 overnight-fasted 健康成年人接受了 150 分钟的 GLP-1(1.2 pmol/kg 体重/分钟)全身输注。在基线和输注 30 和 150 分钟后测定骨骼肌和心肌 MBV(微血管血液体积)、MFV(微血管血流速度)和 MBF(微血管血流)。在 GLP-1 输注前后测量肱动脉直径和平均血流速度,并计算总血流。GLP-1 输注将血浆 GLP-1 浓度升高至餐后水平,并抑制血浆胰高血糖素浓度,同时短暂增加血浆胰岛素浓度。骨骼肌和心肌 MBV 和 MBF 在 30 和 150 分钟时均显著增加(P<0.05)。骨骼肌 MFV 没有变化,但心肌 MFV 略有下降。GLP-1 输注在 150 分钟时显著增加肱动脉直径(P<0.005)和血流速度(P=0.05),导致总肱动脉血流显著增加(P<0.005)。我们的结论是,急性 GLP-1 输注除了舒张健康人中的输送动脉外,还显著募集骨骼肌和心肌微血管。这可能有助于增加组织氧气、营养物质和胰岛素的输送和交换,从而改善人类餐后血糖控制和组织功能。