Mechanisms Mediating the Beneficial Effects of Exercise: Novel Circulating Factors Regulating Metabolism in Human Subjects with Type 2 Diabetes

Physical exercise improves glucose homeostasis in people with type 2 diabetes (T2DM). We and others have found that factors, secreted after exercise into the circulation from skeletal muscle, adipose tissue and other tissues, may regulate glucose metabolism. It is critical to translate these animal-based findings to humans, by identifying novel exercise-stimulated factors in subjects with T2DM, and to understand their function in regulating cell metabolism. I recently spearheaded a project that generated exciting preliminary data revealing the response of 1,310 plasma proteins to an acute exercise bout in healthy lean subjects. We discovered that exercise led to highly-significant, time-specific increases in the plasma concentration of 13% of all the measured circulating proteins, of which the vast majority are novel exercise-regulated proteins. Given the importance of exercise in the treatment of T2DM, it is vital to determine the exercise-induced circulating factor response in T2DM subjects. It will next be essential to determine if these proteins can regulate glucose and fatty acid metabolism. Aims: 1) To determine the effects of a single bout of moderate intensity exercise on plasma protein concentrations of 8 subjects with T2DM. 2) To use bioinformatics to identify exercise-regulated proteins that are differentially regulated by exercise in subjects with T2DM compared to lean. 3) To select the most highly regulated proteins and determine their effects glucose and fatty acid metabolism in vitro. This study will provide critical preliminary data for an RO1 application that will focus on identifying circulating factors as mechanisms mediating the beneficial effects of exercise in subjects with and without T2DM.