Glucagon-like peptide-1 receptor antagonism impairs basal exercise capacity and vascular adaptation to aerobic exercise training in rats.
Glucagon-like peptide-1 receptor antagonism impairs basal exercise capacity and vascular adaptation to aerobic exercise training in rats.
复制标题
胰高血糖素样肽-1受体拮抗作用会损害基础运动能力和对大鼠有氧运动训练的血管适应。
DOI：
10.14814/phy2.13754
复制
发表时间：
2018-07
影响因子：
2.5
通讯作者：
Reusch JEB
中科院分区：
文献类型：
--
作者：
Scalzo RL;Knaub LA;Hull SE;Keller AC;Hunter K;Walker LA;Reusch JEB
呼吸适应性（CRF）与心血管（CV）死亡率呈负相关，2型糖尿病（T2 D）患者的CRF受损。有氧运动训练（ET）改善CRF，并与健康和患病人群中过早死亡的风险降低有关。了解有助于ET适应的机制可以确定降低与T2 D患者相关的CV死亡率的目标。抗高血糖激素胰高血糖素样肽-1（GLP-1）影响许多与运动相同的途径，并可能有助于CV适应ET。我们假设GLP-1是适应ET所必需的。将12周龄雄性Wistar大鼠随机分组（n = 8-12只/组），通过渗透泵接受PBS或GLP-1受体拮抗剂（exendin 9 - 39（Ex（9 - 39）），持续4周± ET。CRF随ET升高而升高（P < 0.01）。Ex（9 - 39）处理使久坐和ET大鼠的CRF减弱（P < 0.001）。Ex（9 - 39）减弱了乙酰胆碱介导的血管舒张，而Ex（9 - 39）+ET维持了这种反应（P = 0.04）。Ex（9 - 39）组的主动脉僵硬度更大（P = 0.057），Ex（9 - 39）与ET组合时更差（P = 0.004）。Ex（9 - 39）的钾和苯丙氨酸的离体主动脉血管收缩较低（P < 0.0001）。用PBS + ET改善颈动脉应变，但在用ET的Ex（9 - 39）大鼠中没有改变（P < 0.0001）。Ex（9 - 39）组左心室线粒体呼吸升高（P < 0.02）。GLP-1受体拮抗剂可损害伴或不伴ET的CRF，减弱血管对ET的适应性，并升高心脏线粒体呼吸。这些数据表明，GLP-1是对ET的适应性血管反应的组成部分。
Cardiorespiratory fitness (CRF) inversely predicts cardiovascular (CV) mortality and CRF is impaired in people with type 2 diabetes (T2D). Aerobic exercise training (ET) improves CRF and is associated with decreased risk of premature death in healthy and diseased populations. Understanding the mechanisms contributing to ET adaptation may identify targets for reducing CV mortality of relevance to people with T2D. The antihyperglycemic hormone glucagon‐like peptide‐1 (GLP‐1) influences many of the same pathways as exercise and may contribute to CV adaptation to ET. We hypothesized that GLP‐1 is necessary for adaptation to ET. Twelve‐week‐old male Wistar rats were randomized (n = 8–12/group) to receive PBS or GLP‐1 receptor antagonist (exendin 9‐39 (Ex(9‐39)) via osmotic pump for 4 weeks ± ET. CRF was greater with ET (P < 0.01). Ex(9‐39) treatment blunted CRF in both sedentary and ET rats (P < 0.001). Ex(9‐39) attenuated acetylcholine‐mediated vasodilation, while this response was maintained with Ex(9‐39)+ET (P = 0.04). Aortic stiffness was greater with Ex(9‐39) (P = 0.057) and was made worse when Ex(9‐39) was combined with ET (P = 0.004). Ex vivo aortic vasoconstriction with potassium and phenylephrine was lower with Ex(9‐39) (P < 0.0001). Carotid strain improved with PBS + ET but did not change in the Ex(9‐39) rats with ET (P < 0.0001). Left ventricular mitochondrial respiration was elevated with Ex(9‐39) (P < 0.02). GLP‐1 receptor antagonism impairs CRF with and without ET, attenuates the vascular adaptation to ET, and elevates cardiac mitochondrial respiration. These data suggest that GLP‐1 is integral to the adaptive vascular response to ET.