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有氧运动训练可减轻Walker 256荷瘤大鼠的肿瘤生长并减少胰岛素分泌。

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats.

作者信息

Moreira Veridiana Mota, da Silva Franco Claudinéia Conationi, Prates Kelly Valério, Gomes Rodrigo Mello, de Moraes Ana Maria Praxedes, Ribeiro Tatiane Aparecida, Martins Isabela Peixoto, Previate Carina, Pavanello Audrei, Matiusso Camila Cristina Ianoni, Almeida Douglas Lopes, Francisco Flávio Andrade, Malta Ananda, Tófolo Laize Peron, da Silva Silveira Sandra, Saavedra Lucas Paulo Jacinto, Machado Katia, da Silva Paulo Henrique Olivieri, Fabrício Gabriel S, Palma-Rigo Kesia, de Souza Helenir Medri, de Fátima Silva Flaviane, Biazi Giuliana Regina, Pereira Taís Susane, Vieira Elaine, Miranda Rosiane Aparecida, de Oliveira Júlio Cezar, da Costa Lima Luiz Delmar, Rinaldi Wilson, Ravanelli Maria Ida, de Freitas Mathias Paulo Cezar

机构信息

Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil.

Department of Physical Education, State University of Maringá, Maringá, Brazil.

出版信息

Front Physiol. 2018 May 8;9:465. doi: 10.3389/fphys.2018.00465. eCollection 2018.

Abstract

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55-65% VO until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training did not cause injury or trigger inflammatory processes prior to tumor cell inoculation. Taken together, the current study suggests that aerobic exercise training applied during adolescence may mitigate tumor growth and related disorders in Walker 256 tumor-bearing adult rats. Improved insulin sensibility, lower glucose and insulin levels and/or reduced insulin secretion stimulated by glucose may be implicated in this tumor attenuation.

摘要

有氧运动训练可以改善许多组织中的胰岛素敏感性;然而,运动、胰岛素和癌细胞生长之间的关系尚不清楚。我们验证了这样一个假设,即在青春期开始的有氧运动训练可以减弱成年大鼠体内Walker 256肿瘤的生长并改变胰岛素分泌。30日龄的雄性Wistar大鼠进行为期8周的跑步机跑步训练,每周3天,每天44分钟,强度为最大摄氧量的55%-65%,直至90日龄(TC,训练对照组)。将相同年龄的一组大鼠在同一时期保持不运动状态(SC,久坐对照组)。然后,将SC组和TC组的动物各一半留作对照,另一半接种Walker 256癌细胞,从而产生另外两组(久坐Walker组和训练Walker组)。在荷瘤大鼠中未观察到死亡。在接种肿瘤细胞前后分析体重(BW)、食物摄入量、血浆葡萄糖、胰岛素水平和外周胰岛素敏感性。我们还评估了肿瘤生长、转移和恶病质。分析了分离的胰岛分泌活性。此外,我们评估了机械敏感性。我们的结果显示,根据最终工作量和最大摄氧量,训练大鼠的体能得到改善,且在跑步训练结束时体重减轻。长期适应有氧运动训练可减轻肿瘤重量、恶病质和转移,并与接种肿瘤细胞前后的低血糖和胰岛素水平以及高胰岛素敏感性相关。年轻时开始的有氧运动还可降低训练大鼠胰岛的胰岛素含量以及葡萄糖刺激后的胰岛素分泌,且不损害胰岛形态。Walker 256荷瘤久坐大鼠的胰岛胰岛素含量也降低,但通过分离胰岛检测的胰岛素分泌未发生变化。机械敏感性测试表明,有氧运动训练在接种肿瘤细胞之前不会造成损伤或引发炎症过程。综上所述,当前研究表明,青春期进行的有氧运动训练可能减轻Walker 256荷瘤成年大鼠的肿瘤生长及相关病症。胰岛素敏感性提高、葡萄糖和胰岛素水平降低和/或葡萄糖刺激的胰岛素分泌减少可能与这种肿瘤减轻有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/836c/5953341/075ab969b6b8/fphys-09-00465-g001.jpg

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