Animal Models of Diabetic Complications Consortium (U01 DK076160) Annual Report (2009) “Mitochondrial SOD as a Target for Diabetic Neuropathy” University of Michigan Principal Investigator Eva L. Feldman, M.D., Ph.D. Address: University of Michigan Department of Neurology 109 Zina Pitcher Road 5017 BSRB Ann Arbor MI 48109-2200 Phone: (734) 763-7274 E-mail:
[email protected] 1 Table of Contents Page Part A: Principal Investigator’s Summary 3-21 1. Project Accomplishments (2009) 4-13 2. Collaboration 13-15 3. Address previous EAC comments 15-19 4. Publications 19-20 Part B: Individual Project Reports by Responsible Investigator (if applicable) NA 2 Animal Models of Diabetic Complications Consortium (U01 DK076160) Part A: Principal Investigator’s Summary 3 1. Program Accomplishments: Hypothesis: We continue to investigate the damaging effects of diabetes-induced oxidative stress on the nervous system. Our primary goal is examining the onset and progression of diabetic polyneuropathy (DPN). Recent data collected from our archived human samples indicates that elevated triglycerides predict the progression of DPN in human patients (1). We have confirmed the damaging effects of oxidized lipids on neuronal oxidative stress and DPN progression in an animal model of type 2 diabetes, high fat fed C57Bl/6J mice (2). We are also investigating the role of diabetes induced oxidative stress, dyslipidemia and insulin resistance on neurons of the central nervous system with regard to the pathology of Alzheimer’s disease. The results of these two studies are detailed below. Progress Towards Stated Milestones: Dyslipidemia-Induced Neuropathy in Mice We investigated the impact of a high fat diet on the induction of insulin resistance, dyslipidemia and neuropathy in C57Bl/6J mice.