Neurovascular Research Laboratory, School of Kinesiology, The University of Western Ontario, London, Ontario, Canada;
Exercise Biochemistry Laboratory, School of Kinesiology, The University of Western Ontario, London, Ontario, Canada;
Am J Physiol Regul Integr Comp Physiol. 2014 Jun 15;306(12):R941-50. doi: 10.1152/ajpregu.00508.2013. Epub 2014 Apr 16.
Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.
胰岛素通过一氧化氮合酶（NOS）机制刺激神经动脉血管舒张。实验性糖尿病会降低神经血管内的一氧化氮反应性。研究高血糖和神经动脉血管舒张的实验通常会省略胰岛素治疗，并使用久坐的大鼠，导致严重的高血糖。我们检验了以下两个假设：1）胰岛素治疗的实验性糖尿病和不活动（DS 大鼠）会减弱胰岛素介导的神经动脉血管舒张，以及 2）DS 大鼠的血管舒张缺陷将通过同时进行的运动训练（DX 大鼠；75-85%最大摄氧量，每天 1 小时，每周 5 天，持续 10 周）得到克服。血管传导值（VCi=神经血流速度/平均动脉血压）的基线指数相似（P≥0.68），但在正常血糖高胰岛素钳夹（EHC；10mU·kg(-1)·min(-1)）期间，峰值 VCi 和 VCi 曲线下面积（AUCi）在 DS 大鼠中低于对照久坐（CS）大鼠和 DX 大鼠（P≤0.01）。运动神经传导速度（MNCV）在 DS 大鼠中低于 CS 大鼠和 DX 大鼠（P≤0.01）。与 DS 大鼠相比，DX 大鼠的神经内皮型一氧化氮合酶（eNOS）蛋白含量更高（P=0.04）。在另一项分析中，我们研究了单独的糖尿病对运动训练大鼠的影响。与运动训练的对照大鼠（CX）相比，DX 大鼠在 EHC 期间的 AUCi 较低，MNCV 值较低，坐骨神经 eNOS 蛋白含量较低（P≤0.03）。因此，DS 大鼠的神经血管和运动神经功能受损。患有糖尿病的大鼠的这些缺陷可以通过同时进行的运动训练来克服。然而，在运动训练的大鼠（CX 和 DX 组）中，中度高血糖会降低神经血管和神经功能。
