The primary research efforts of the Diabetes Center faculty can be divided into 6 interactive and interrelated areas of emphasis that encompass both type 1 (T1DM) and type 2 (T2DM) diabetes and related metabolic defects. These investigations cover the spectrum from basic molecular mechanisms of cell function, integrative system physiology and pre-clinical studies to clinical and community-based translational research. We have grouped our major research directions into six thematic research clusters.
Islet Biology & Immunology
The beta cell group members are studying:
- the genetic and molecular biological bases of the proliferation of insulin production of beta cells as well as other islet cells
- innovative and non-invasive approaches to ascertain beta cell mass
- structural basis for T-cell signaling and the immune pathogenesis of T1DM
- functional beta cell regeneration
- molecular pathways regulating glucose/secretagogue-stimulated insulin secretion
- novel approaches for islet cell transplantation
Signal transduction investigators are elucidating mechanisms that govern target cell responses to hormones and growth factors. Modulation of hormonal responses by cytokines, metabolites and cell-cell interactions are central topics of investigation. Major interests include initiation, propagation and termination of the insulin signal, signaling by counter-regulatory hormones, and the origin and consequences of co-stimulatory interactions between insulin responsive tissues and inflammatory cells that occur in obesity, diabetes and related pathologies that can lead to dysregulated glucose and lipid metabolism. Delineation of insulin signal transduction and other interacting signaling pathways utilized by various cells to elicit distinct biological responses is key to understanding altered metabolism in insulin resistant and diabetic states. This group of ES-DRC investigators examines integration and signaling crosstalk between various transduction pathways mediating glucose transport, fatty acid synthesis/secretion and storage, nutrient sensing, vesicle trafficking and protein synthesis.
Central and Peripheral Regulation of Metabolism
The dramatic increase in the prevalence of T2DM in developed and developing countries is causally linked with the geographically and temporally overlapping epidemic of obesity, but our understanding of how obesity leads to diabetes is still limited. The ES-DRC continues to play a critical role in the investigation of the basic mechanisms responsible for this association. In keeping with the collaborative spirit that defines the ES-DRC, this work is the product of synergistic interactions among investigators. The ES-DRC provides the scientific environment as well as critical resources and expertise to support projects, which operate under the basic premise that an imbalance between caloric intake and energy expenditure triggers endocrine/metabolic responses that accelerate dysregulation in glucose and lipid metabolism.
All forms of diabetes are characterized by hyperglycemia, a relative or absolute lack of insulin action, and the development of diabetes-specific pathology 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, it is now clear that the diabetes and obesity epidemic is driving additional complications. For example, diabetes and obesity are associated with higher risks of certain cancers and the increased prevalence of obesity-associated asthma has distinct molecular features from classical asthma. ES-DRC faculty are actively studying these important areas that encompass the molecular, cellular, tissue and integrative physiologic aspects of diabetes sequelae.
Metabolic Patient-Oriented Research & Diabetes-Focused Clinical Trials
The ES-DRC has long-standing recognition as an exceptional national site for patient-oriented metabolic research and diabetes-focused clinical trials, including the landmark DCCT and DPP studies and the more recently the Glycemia Reduction Approaches in Diabetes (GRADE), which is a comparative effectiveness study directly comparing four classes of commonly used diabetes medications (in combination with metformin) in a "real world" setting. In addition, ES-DRC investigators perform patient-oriented research studies to address important questions that cannot be answered in animal or cell model systems. These studies include developing novel ways to improve treatment of type 1 diabetes, studying the etiology of hypoglycemia unawareness, exploring the integrated regulation of hepatic glucose production and sensitivity of peripheral tissues to insulin.
Social-Environmental Determinants of Metabolic Health
Prevention and control of diabetes and its complications are determined, in part, by social, psychological and environmental factors. Here, we have multi-disciplinary scientists engaged in methodological approaches to move studies forward toward translation into the community. These investigators use epidemiologic research, community-based participatory research as well as randomized controlled trials to study:
- prevention of type 2 diabetes and its complications
- translation of intervention to the community
- psychological determinants of metabolic health
- issues related to health care for pediatric type 1 or type 2 diabetes