The overall theme of my research is the role of the nervous system in autonomic control. Our most recent studies have focused on autonomic control of the heart, and specifically, the heart valves. The purpose of this project is (1) to determine the relationship between damage to nerves (neuropathy) and damage to the heart valves (with focus on the mitral valve), which occurs with increased frequency in patients with diabetes; and (2) to investigate how diabetes leads to development of neuropathy and mitral valve damage. The proposed project uses techniques from several different areas of research and medicine (immunohistochemical confocal microscopy, in vitro organ bath physiology/pharmacology, echocardiography, etc.) and an animal model that has been studied and established as having features of both type 1 and type 2 diabetes. These techniques and model enable us to carry out an innovative, systematic investigation of (1) changes caused by diabetes in the structure and function of the mitral valve and the nerves that supply it and (2) whether and how these changes may respond to experimental and potential therapies. The ultimate goal is that this information will provide strategies for testing and developing effective therapies for diabetes and the complications of diabetic neuropathy that can be applied to patients.