The roles of muscle contraction and insulin on restoring glucose uptake with novel pharmaceutical and engineering solutions

在航天飞行中，宇航员循环中的胰岛素和葡萄糖水平升高，表明胰岛素抵抗的发展。航天期间胰岛素抵抗的短期和长期发展的后果尚不清楚，但将对全身健康产生有害影响。因此，制定在太空飞行期间保持胰岛素敏感性的策略是非常重要的，特别是在有可能进行像火星这样的长期航行的情况下。利用卧床休息或固定模型的研究表明，胰岛素抵抗迅速发作，并表明肌肉收缩的减少主要是导致葡萄糖处置不足的原因。肌肉负荷和胰岛素的作用是肌肉摄取葡萄糖的强大驱动因素，随着宇航员暴露在长时间的肌肉卸载中，这可能为开发新的干预措施提供途径。目标：1-该项目将利用现有的制动引起的肌肉萎缩样本来测量葡萄糖代谢的变化，并进行无标签蛋白质组分析，以调查肌肉和血浆蛋白质的变化。2-利用单侧手臂制动模型进行一项研究，以研究恢复制动引起的胰岛素抵抗的策略。在这项研究中，我们将a.调查抗糖尿病药物的效果，并期待重新定位药物以防止固定化对葡萄糖处置的影响。此外，我们将与药房合作，寻求开发新的药物干预措施。3-由于已知肌肉收缩和阻力运动可以增加和恢复胰岛素敏感性，我们将调查恢复胰岛素敏感性所需的最低运动量。我们将通过与工程学院合作开发一种适合在太空飞行中使用的新型锻炼设备来实现这一点。

During spaceflight astronauts display increased levels of circulating insulin and glucose demonstrating the development of insulin resistance. The consequences of short- and long-term development of insulin resistance during spaceflight are unclear but will have deleterious effects on whole body health. As such, the development of strategies to maintain insulin sensitivity during spaceflight is of great importance, particularly with the possibility of long-term voyages such as to mars. Studies utilizing bed rest or models of immobilisation have demonstrated a rapid onset of insulin resistance and suggest that a reduction in muscle contraction is primarily driving deficits in glucose disposal. Muscle loading and the actions of insulin are powerful drivers of glucose uptake into muscle and with astronauts exposed to prolonged periods of muscle unloading, may offer avenues to develop novel interventions. Aims:1- This project will utilize existing samples of immobilisation induced muscle atrophy to measure altered glucose metabolism and perform label free proteomic analysis to investigate alterations in both the muscle and plasma proteome.2- Undertake a study utilizing a unilateral arm immobilisation model to investigate strategies to restore immobilisation induced insulin resistance. During this study we will a. Investigate the effects of antidiabetic drugs and look to re-purpose drugs to protect against immobilisation induced effects on glucose disposal.b. Further, in collaboration with pharmacy, we will look to develop novel pharmaceutical interventions.3- With muscle contraction and resistance exercise known to increase and restore insulin sensitivity, we will investigate what is the minimum amount of exercise needed to restore insulin sensitivity. We will do this through the development of a novel exercise device in collaboration with the school of engineering that is suitable for use during space flight.