PROJECT SUMMARY – PHYSIOLOGY CORE Physiological research in humans and animal models has been an integral part of the Chicago Diabetes Research and Training Center (DRTC) since its inception. The mission of the Physiology Core is to provide DRTC investigators with the tools and knowledge necessary to investigate the pathophysiology of diabetes and its effects on metabolically active tissues. An important evolution of this Core is the inclusion of detailed metabolic phentopying services and circadian rhythm services based at Northwestern University. This new collaborative working relationship between the University of Chicago and Northwestern University adds value to the DRTC by providing access to an array of both state-of-the-art and unique resources, technology and services that are not otherwise available through core facilities at any of the DRTC affiliated institutions. The long-range objectives and goals of this Core are to understand the pathophysiology of diabetes and its complications. The Core serves both experienced as well as novice users and functions as an important conduit for facilitating entry into the field for investigators who have not traditionally performed metabolic physiology research. In addition to consultative and experimental services, the Core provides training for investigators who wish to incorporate specialized techniques back into their own lab. The Core provides advice and hands-on-training to investigators in clinical studies of non-diabetic and diabetic humans, physiology studies of mice and mouse, mouse model generation, and cellular physiology studies. The Specific Aims of the Core are to provide advice, training, and service in each of the following areas: 1. Clinical studies of non-diabetic and diabetic human subjects. 2. Large-scale analysis of pancreatic beta-cell mass, islet size distribution, islet cellular composition and islet vasculature in the human and mouse pancreas 3. Comprehensive metabolic phenotyping of mice. 4. Generation of specialized mouse models that span disorders of metabolism and glucose. 5. Cellular physiology services, including bioenergetic analyses, metabolic flux labeling, and measurement of adenine nucleotides 6. Studies of the role of the microbiome on diabetes and obesity.