Research Areas Research within the Einstein-Mount Sinai Diabetes Researcher Center (ES-DRC) falls into six categories: Islet Biology & Immunology Members of this team collaborate on studies of various aspects of islet biology, with a focus on: understanding the basis for impaired glucose-stimulated insulin secretion and beta cell proliferation; the cellular and molecular pathways responsible for autoimmune activation; and ultimate elimination/loss of islet beta cells, with the goal of increasing beta cell mass and function. In these approaches, our team is developing imaging procedures and islet transplantation approaches to assess beta cell mass in vivo. In addition, our researchers are elucidating the molecular basis for the immune pathogenesis of type 1 diabetes in order to selectively suppress beta cell autoimmune attack. Using this information, along with the structural basis for T-cell signaling, this group has developed a novel technology to suppress beta cell–specific T-cell autoimunnity. Signal Transduction Investigators in this research program explore the mechanisms that govern how cells respond to hormones and other extracellular factors that directly regulate metabolism. Topics of investigation include the regulatory networks controlled by insulin, glucagon (a pancreatic hormone that raises glucose and fatty acid levels in the blood), cytokines (cell-signaling molecules), and various substances secreted by adipose (fat) tissue. Other research interests include how counter-regulatory hormones (hormones that have opposite effects) initiate, maintain, and stop insulin signaling and the interactions between insulin-responsive tissues and inflammatory cells that occur in obesity, diabetes, and related metabolic diseases. In particular, major efforts are focused on the various pathways that mediate glucose transport; fatty acid synthesis, secretion, and storage; nutrient sensing; and protein synthesis. Understanding these and other signaling pathways are key to our understanding altered metabolism in various insulin resistance and diabetic states. Central and Peripheral Regulation of Metabolism The dramatic increase in the prevalence of type 2 diabetes in developed and developing countries has been linked to the epidemic of obesity, but how obesity leads to diabetes is still not clear. Investigators is this group are studying the basic mechanisms linking diabetes and obesity, based on the premise that an imbalance between caloric intake and energy expenditure triggers endocrine/metabolic responses that accelerate dysregulation of glucose and lipid metabolism. Diabetic Complications Members of this group study the molecular, cellular, tissue, and integrative physiologic aspects of diabetes complications. All forms of diabetes are characterized by hyperglycemia (a relative or absolute lack of insulin action) and the development of diabetes-specific disease in the retina, renal glomerulus, and peripheral nerves. Diabetes is also associated with accelerated atherosclerotic disease affecting arteries that supply the heart, brain, and lower extremities. In addition to these classical complications, the intertwined diabetes and obesity epidemics are driving additional complications, such as a heightened risk for cancer and an increased prevalence of obesity-associated asthma (which has distinct molecular features from classical asthma). Metabolic Patient-Oriented Research & Diabetes-Focused Clinical Trials The ES-DRC is a nationally recognized site for patient-oriented metabolic research and diabetes-focused clinical trials, including the landmark Diabetes Control and Complications Trial (DCCT), the Diabetes Prevention Program (DPP) and, more recently, the Glycemia Reduction Approaches in Diabetes (GRADE), which compared four classes of commonly used diabetes medications (in combination with metformin) in real-world settings. In addition, ES-DRC investigators perform patient-oriented research studies to address important questions that cannot be answered in animal or cell model systems. Our researchers are currently studying new ways to improve type 1 diabetes treatment, the etiology of hypoglycemia unawareness, and the integrated regulation of hepatic glucose production and sensitivity of peripheral tissues to insulin. Social-Environmental Determinants of Metabolic Health Our multidisciplinary scientists study the social, psychological, and environmental factors that affect the prevention and control of diabetes and its complications. These investigators are epidemiologic research, community-based participatory research, and randomized controlled trials to study: the prevention of type 2 diabetes and its complications, translation of interventions to the community, psychological determinants of metabolic health, and issues related to care of patients with pediatric type 1 or type 2 diabetes.