Dept. of Anatomy, Cellular Biology and Biophysics and Physiology, Institute of Biology, State Univ. of Campinas (UNICAMP). P.O. Box 6109, Campinas, SP. CEP: 13083-865, Brazil.
J Appl Physiol (1985). 2012 Mar;112(5):711-8. doi: 10.1152/japplphysiol.00318.2011. Epub 2011 Dec 15.
Endurance training has been shown to increase pancreatic β-cell function and mass. However, whether exercise modulates β-cell growth and survival pathways signaling is not completely understood. This study investigated the effects of exercise on growth and apoptotic markers levels in rat pancreatic islets. Male Wistar rats were randomly assigned to 8-wk endurance training or to a sedentary control group. After that, pancreatic islets were isolated; gene expression and the total content and phosphorylation of several proteins related to growth and apoptotic pathways as well as the main antioxidant enzymes were determined by real-time polymerase chain reaction and Western blot analysis, respectively. Reactive oxygen species (ROS) production was measured by fluorescence. Endurance training increased the time to reach fatigue by 50%. Endurance training resulted in increased protein phosphorylation content of AKT (75%), AKT substrate (AS160; 100%), mTOR (60%), p70s6k (90%), and ERK1/2 (50%), compared with islets from control group. Catalase protein content was 50% higher, whereas ROS production was 49 and 77% lower in islets from trained rats under basal and stimulating glucose conditions, respectively. Bcl-2 mRNA and protein levels increased by 46 and 100%, respectively. Bax and cleaved caspase-3 protein contents were reduced by 25 and 50% in islets from trained rats, respectively. In conclusion, these results demonstrate that endurance training favors the β-cell growth and survival by activating AKT and ERK1/2 pathways, enhancing antioxidant capacity, and reducing ROS production and apoptotic proteins content.
耐力训练已被证明可以增加胰腺β细胞的功能和数量。然而,运动是否调节β细胞生长和存活途径信号尚未完全清楚。本研究探讨了运动对大鼠胰岛生长和凋亡标志物水平的影响。雄性 Wistar 大鼠被随机分为 8 周耐力训练组或久坐对照组。之后,分离胰岛;通过实时聚合酶链反应和 Western blot 分析分别测定与生长和凋亡途径相关的基因表达以及几种蛋白质的总含量和磷酸化水平,以及主要抗氧化酶。通过荧光测量活性氧(ROS)的产生。耐力训练将疲劳时间延长了 50%。与对照组相比,耐力训练使 AKT(75%)、AKT 底物(AS160;100%)、mTOR(60%)、p70s6k(90%)和 ERK1/2(50%)的蛋白磷酸化含量增加。与基础和刺激葡萄糖条件下的对照组相比,CAT 蛋白含量高 50%,ROS 产生分别低 49%和 77%。Bcl-2 mRNA 和蛋白水平分别增加了 46%和 100%。Bax 和 cleaved caspase-3 蛋白含量分别降低了 25%和 50%。总之,这些结果表明,耐力训练通过激活 AKT 和 ERK1/2 途径、增强抗氧化能力以及减少 ROS 产生和凋亡蛋白含量,有利于β细胞的生长和存活。