The aim of the Analytical Core (RC3) is to provide analytical support for RCDC investigators and pilot projects that utilize stable isotope tracers. We have provided the technical advice necessary to obtain administrative approval and approval of the Institutional Review Board to enable the pilot studies to move forward. The necessary analyses have been fine-tuned for bulk sampling as soon as samples are collected. One pilot study funded by the institution is well underway and the analytical and computational methods needed to perform the study have been worked out. We have supported the development and are now supporting the execution of a pilot study investigating the role of the amino acid lysine in ameliorating insulin resistance in elderly individuals. We have developed the method to quantify hepatic glucose production and peripheral glucose uptake in the context of a protocol that does not include the infusion of insulin. This approach enables the quantification of the extent of insulin release in response to hyperglycemia, which is an important parameter not obtained using the traditional euglycemic clamp approach. We have all methods in place to quantify arginine and nitric oxide synthesis in human subjects, and have just started measuring samples for this pilot project. The development of new pilot studies involving the metabolic response in congestive heart failure has also been supported. Our focus has primarily been on the development of methods to quantify intracellular trafficking of fatty acids in live and particularly muscle (see publications below). These methods are being incorporated into new proposals for consideration of pilot funding. We have also established the analytical and computational approach needed to perform the multi-tracer approach to quantifying insulin sensitivity and insulin release in response to ingestion of a bolus of bolus of glucose. This method is now being used in an institutionally- sponsored pilot project investigating the role of lysine supplementation in ameliorating insulin resistance in the elderly. Efforts have been successful to recruit young investigators within the institution and to also expand our base of young investigators throughout the state of Arkansas. The Tracer Methodology Course (see below) has provided a good pool of potential new investigators, and we have recently recruited Dr. IL-Young Kim via that route to be trained in the Geriatrics Department as an investigator in muscle protein metabolism in elderly. Within the institution, Jamie Harrison, MD, spent the research component of her residency program in physical medicine working full time within the group being trained in the performance of stable isotope tracer studies of muscle metabolism in elderly. Ricki Fram, MD, continues to work within the context of the Pepper Center as she completes her cardiology fellowship. We are also developing collaborations with young investigators at other institutions in Arkansas who previously have had no availability to the technology to perform stable isotope tracer experiment. Cody Sipe, PhD, is a recently appointed Assistant Professor at Harding University and he is actively involved in ongoing projects, as well as future plans. He is submitting a proposal for a pilot study to the Pepper grant, and is involved in the preparation of a program project proposal focused on muscle metabolism and congestive heart failure. Jamie Baum, PhD, experienced in mitochondrial function in muscle has her primary appointment at the University of Arkansas at Fayetteville. She and her colleagues in the Muscle Research Group at UA have visited the Pepper Center in Little Rock to explore ways in which active collaboration can be stimulated, with the result of enabling investigators at the UA campus to incorporate stable isotope tracer studies into their studies of muscle metabolism, and to focus their research more to the area of alterations that occur with aging. We completed the course on Tracer Methodology the week of March 12-16, 2011 in Little Rock. Seventy-two investigators attended the week-long course, which consisted of didactic lectures, workshops, and one-on-one sessions. The primary focus of the course is the performance of stable isotope tracer studies, including analysis of enrichment and calculations associated with relevant modeling.