McDonald Matthew W, Olver T Dylan, Dotzert Michelle S, Jurrissen Thomas J, Noble Earl G, Padilla Jaume, Melling Cw James
1 School of Kinesiology, Western University, London, ON, Canada.
2 Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Diab Vasc Dis Res. 2019 Jan;16(1):77-86. doi: 10.1177/1479164118815279. Epub 2018 Dec 11.
Vascular insulin resistance often precedes endothelial dysfunction in type 1 diabetes mellitus. Strategies to limit vascular dysfunction include intensive insulin therapy (4-9 mM) and aerobic training. To avoid the risk of hypoglycaemia, individuals often prescribed conventional insulin therapy (9-15 mM) and participate in resistance training. In a model of type 1 diabetes mellitus, this study examined insulin-induced vasomotor function in the aorta and femoral artery to determine (1) whether resistance training with conventional insulin therapy provides the same benefits as aerobic training with conventional insulin therapy, (2) whether aerobic training or resistance training, when paired with conventional insulin therapy, results in superior vasomotor function compared to intensive insulin therapy alone and (3) whether vessel-specific adaptations exist. Groups consisted of conventional insulin therapy, intensive insulin therapy, aerobic training with conventional insulin therapy and resistance training with conventional insulin therapy. Following multiple low doses of streptozotocin, male Sprague-Dawley rats were supplemented with insulin to maintain blood glucose concentrations (9-15 mM: conventional insulin therapy, aerobic training and resistance training; 4-9 mM: intensive insulin therapy) for 12 weeks. Aerobic training performed treadmill exercise and resistance training consisted of weighted climbing. Coinciding with increased Akt signalling, aerobic training resulted in enhanced insulin-induced vasorelaxation in the femoral artery. Intensive insulin therapy displayed increased mitogen-activated protein kinase signalling and no improvement in insulin-stimulated vasorelaxation compared to all other groups. These data suggest that aerobic training may be more beneficial for limiting the pathogenesis of vascular disease in type 1 diabetes mellitus than merely intensive insulin therapy.
在1型糖尿病中,血管胰岛素抵抗通常先于内皮功能障碍出现。限制血管功能障碍的策略包括强化胰岛素治疗(4-9毫摩尔)和有氧运动训练。为避免低血糖风险,个体常采用传统胰岛素治疗(9-15毫摩尔)并参与抗阻训练。在1型糖尿病模型中,本研究检测了胰岛素诱导的主动脉和股动脉血管舒缩功能,以确定:(1)传统胰岛素治疗联合抗阻训练是否与传统胰岛素治疗联合有氧运动训练具有相同益处;(2)传统胰岛素治疗联合有氧运动训练或抗阻训练时,与单独强化胰岛素治疗相比,是否能产生更优的血管舒缩功能;(3)是否存在血管特异性适应性变化。分组包括传统胰岛素治疗组、强化胰岛素治疗组、传统胰岛素治疗联合有氧运动训练组和传统胰岛素治疗联合抗阻训练组。多次低剂量链脲佐菌素处理后,给雄性斯普拉格-道利大鼠补充胰岛素以维持血糖浓度(9-15毫摩尔:传统胰岛素治疗、有氧运动训练和抗阻训练;4-9毫摩尔:强化胰岛素治疗)12周。有氧运动训练采用跑步机运动,抗阻训练包括负重攀爬。与Akt信号增加一致,有氧运动训练使股动脉中胰岛素诱导的血管舒张增强。与所有其他组相比,强化胰岛素治疗显示有丝分裂原活化蛋白激酶信号增加,且胰岛素刺激的血管舒张无改善。这些数据表明,对于限制1型糖尿病血管疾病的发病机制,有氧运动训练可能比单纯强化胰岛素治疗更有益。