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

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.