Stine Søndergaard - The overarching research focus of the project is the production of reactive oxygen species (ROS) in skeletal muscle of patients with T2D

Excessive chronic production of ROS is associated with skeletal muscle insulin resistance. Glutathione is the most abundant endogenous antioxidant in the cell and thus, a crucial protector against ROS and insulin resistance. Based on previous studies, we speculate that glutathione supplementation improves skeletal muscle insulin sensitivity and that this effect may be ascribed to a reduced level of ROS.

By contrast, transient ROS production in response to exercise is associated with mitochondrial biogenesis. Some patients with T2D have a diminished training-induced mitochondrial biogenesis. The reason for this defect is not known, but we speculate that lower exercise intensity, leading to a lower exercise-stimulated ROS production, is a more optimal stimulus for mitochondrial biogenesis in patients with T2D. 

To gain a more thorough understanding of ROS production in patients with T2D and to identify if and how different interventions may improve the treatment of diabetes, this project aims to answer the following research questions: 

1. Does oral glutathione supplementation improve skeletal muscle insulin sensitivity in patients with T2D. If so, can this effect be linked to a more beneficial redox state in the muscle?
   
   
2. Does the exercise-induced increased ROS production required for mitochondrial biogenesis response differs between patients with T2D and healthy controls? If so, does low intensity exercise reduce the transient production of ROS and thus, result in a higher mitochondrial biogenesis response in patients with T2D, compared to exercise at high intensity?