Borges Mariana Eiras, Ribeiro Alessandra Mussi, Pauli José Rodrigo, Arantes Luciana Mendonça, Luciano Eliete, de Moura Leandro Pereira, de Almeida Leme José Alexandre Curiacos, Medeiros Alessandra, Bertolini Natália Oliveira, Sibuya Clarice Yoshiko, Gomes Ricardo José
Department of Biosciences, São Paulo Federal University (UNIFESP), Santos, São Paulo, Brazil.
Sport Science Course, University of Campinas, UNICAMP, Limeira, São Paulo, Brazil.
Neurosci Lett. 2017 Feb 3;639:157-161. doi: 10.1016/j.neulet.2016.12.059. Epub 2016 Dec 26.
The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol. Wistar rats were distributed in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32mg/kgb.w.). The training program consisted in swimming 5days/week, 1h/day, during 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. At the end, cerebellum was extracted to determinate the protein expression of GSK-3β, IRβ and IGF-1R and the phosphorylation of β-amyloid, Tau, ERK1+ERK2 by Western Blot analysis. All dependent variables were analyzed by one-way analysis of variance with significance level of 5%. Diabetes causes hyperglycemia in both diabetic groups; however, in TD, there was a reduction in hyperglycemia compared to SD. Diabetes increased Tau and β-amyloid phosphorylation in both SD and TD groups. Furthermore, aerobic exercise increased ERK1+ERK2 expression in TC. The data showed that in cerebellum of diabetic rats induced by alloxan there are some proteins expression like Parkinson cerebellum increased, and the exercise training was not able to modulate the expression of these proteins.
糖尿病(DM)是一种与小脑等脑区损伤相关的慢性疾病,会增加患帕金森病(PD)等神经退行性疾病的风险。在糖尿病和帕金森病动物的大脑中,胰岛素/胰岛素样生长因子-1(IGF-1)信号通路发生改变。运动训练是预防神经退行性疾病的有效干预措施,因为它能释放神经营养因子并调节大脑中的胰岛素/IGF-1信号通路。本研究旨在评估接受运动训练方案的糖尿病大鼠小脑中参与胰岛素/IGF-1通路的蛋白质。将Wistar大鼠分为四组:久坐对照组(SC)/训练对照组(TC)、久坐糖尿病组(SD)和训练糖尿病组(TD)。用四氧嘧啶(ALX)(32mg/kg体重)诱导糖尿病。训练方案包括每周游泳5天,每天1小时,持续6周,负荷相当于无氧阈值的90%。最后,提取小脑,通过蛋白质免疫印迹分析测定糖原合酶激酶-3β(GSK-3β)、胰岛素受体β亚基(IRβ)和IGF-1受体(IGF-1R)的蛋白质表达以及β淀粉样蛋白、 Tau蛋白、细胞外信号调节激酶1+细胞外信号调节激酶2(ERK1+ERK2)的磷酸化水平。所有因变量均采用单因素方差分析,显著性水平为5%。糖尿病在两个糖尿病组中均导致高血糖;然而,与SD组相比,TD组的高血糖有所降低。糖尿病在SD组和TD组中均增加了Tau蛋白和β淀粉样蛋白的磷酸化水平。此外,有氧运动增加了TC组中ERK1+ERK2的表达。数据表明,在四氧嘧啶诱导的糖尿病大鼠小脑中,存在一些类似帕金森病小脑的蛋白质表达增加的情况,而运动训练无法调节这些蛋白质的表达。