2 型糖尿病患者在缺氧和运动期间骨骼肌灌注减少和 ATP 释放受损。
Reduced skeletal-muscle perfusion and impaired ATP release during hypoxia and exercise in individuals with type 2 diabetes.
机构信息
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Winslowparken 21 3, 5000, Odense, Denmark.
Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
出版信息
Diabetologia. 2019 Mar;62(3):485-493. doi: 10.1007/s00125-018-4790-0. Epub 2019 Jan 3.
AIMS/HYPOTHESIS: Plasma ATP is a potent vasodilator and is thought to play a role in the local regulation of blood flow. Type 2 diabetes is associated with reduced tissue perfusion. We aimed to examine whether individuals with type 2 diabetes have reduced plasma ATP concentrations compared with healthy control participants (case-control design).
METHODS
We measured femoral arterial and venous plasma ATP levels with the intravascular microdialysis technique during normoxia, hypoxia and one-legged knee-extensor exercise (10 W and 30 W) in nine participants with type 2 diabetes and eight control participants. In addition, we infused acetylcholine (ACh), sodium nitroprusside (SNP) and ATP into the femoral artery to assess vascular function and ATP signalling.
RESULTS
Individuals with type 2 diabetes had a lower leg blood flow (LBF; 2.9 ± 0.1 l/min) compared with the control participants (3.2 ± 0.1 l/min) during exercise (p < 0.05), in parallel with lower venous plasma ATP concentration (205 ± 35 vs 431 ± 72 nmol/l; p < 0.05). During systemic hypoxia, LBF increased from 0.35 ± 0.04 to 0.54 ± 0.06 l/min in control individuals, whereas it did not increase (0.25 ± 0.04 vs 0.31 ± 0.03 l/min) in the those with type 2 diabetes and was lower than in the control individuals (p < 0.05). Hypoxia increased venous plasma ATP levels in both groups (p < 0.05), but the increase was higher in control individuals (90 ± 26 nmol/l) compared to those with type 2 diabetes (18 ± 5 nmol/l). LBF and vascular conductance were lower during ATP (0.15 and 0.4 μmol min [kg leg mass]) and ACh (100 μg min [kg leg mass]) infusion in individuals with type 2 diabetes compared with the control participants (p < 0.05), whereas there was no difference during SNP infusion.
CONCLUSIONS/INTERPRETATION: These findings demonstrate that individuals with type 2 diabetes have lower plasma ATP concentrations during exercise and hypoxia compared with control individuals, and this occurs in parallel with lower blood flow. Moreover, individuals with type 2 diabetes have a reduced vasodilatory response to infused ATP. These impairments in the ATP system are both likely to contribute to the reduced tissue perfusion associated with type 2 diabetes.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02001766.
目的/假设：血浆 ATP 是一种有效的血管舒张剂，被认为在局部血流调节中发挥作用。2 型糖尿病与组织灌注减少有关。我们旨在研究与健康对照组参与者相比，2 型糖尿病患者的血浆 ATP 浓度是否降低（病例对照设计）。
方法
我们使用血管内微透析技术在 9 名 2 型糖尿病患者和 8 名对照组参与者的正常氧、低氧和单腿伸膝运动（10 W 和 30 W）期间测量股动脉和静脉血浆 ATP 水平。此外，我们向股动脉输注乙酰胆碱（ACh）、硝普钠（SNP）和 ATP，以评估血管功能和 ATP 信号。
结果
与对照组参与者（3.2±0.1 l/min）相比，2 型糖尿病患者在运动期间的下肢血流量（LBF；2.9±0.1 l/min）较低（p<0.05），同时静脉血浆 ATP 浓度也较低（205±35 与 431±72 nmol/l；p<0.05）。在全身低氧期间，对照组个体的 LBF 从 0.35±0.04 增加到 0.54±0.06 l/min，而 2 型糖尿病患者的 LBF 并未增加（0.25±0.04 与 0.31±0.03 l/min），并且低于对照组（p<0.05）。低氧增加了两组的静脉血浆 ATP 水平（p<0.05），但对照组的增加幅度更高（90±26 nmol/l），而 2 型糖尿病患者的增加幅度较低（18±5 nmol/l）。与对照组相比，2 型糖尿病患者在输注 ATP（0.15 和 0.4 μmol min [kg 下肢质量]）和 ACh（100 μg min [kg 下肢质量]）期间的 LBF 和血管传导率较低（p<0.05），而在输注 SNP 期间没有差异。
结论/解释：这些发现表明，与对照组相比，2 型糖尿病患者在运动和低氧期间的血浆 ATP 浓度较低，这与较低的血流量同时发生。此外，2 型糖尿病患者对输注的 ATP 的血管舒张反应降低。ATP 系统的这些损伤可能都有助于与 2 型糖尿病相关的组织灌注减少。
试验注册
ClinicalTrials.gov NCT02001766。
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