Hyperglycemia mediates sarcomeric mechanical function in cardiac and skeletal muscle

Hyperglycemia has been associated with cardiac diastolic dysfunction, which is characterized by impaired relaxation. Specific mechanisms underlying hyperglycemia-induced diastolic dysfunction are unclear. In addition to cardiac sequelae, people with diabetes also report declines in skeletal muscle function, but it is not known if relaxation is altered in skeletal muscle. While aspects of regulation and function are unique between skeletal and cardiac muscle, there is a commonality between the two systems in the organization of the sarcomeres and how the sarcomeric proteins interact to generate force and how they relax. By studying the function of small bundles of sarcomeres (myofibrils), differences in relaxation can be defined. We hypothesize that hyperglycemia alters cardiac and skeletal sarcomeric mechanical function leading to prolonged relaxation. This proposal outlines an innovative concept that sarcomeric function is similarly altered in hearts and skeletal muscles in response to hyperglycemia. If skeletal muscle sarcomeric function is similarly modified by hyperglycemia as cardiac sarcomeric function, it is possible that less invasive biopsies of skeletal muscle may be a mechanism of assessing cardiac sarcomeric function prior to overt organ functional changes.