The purpose of our research is to understand how glucose stimulates insulin secretion by pancreatic islet cells and to characterize and reverse abnormalities in this process that are present in diabetes. Insulin secretion by pancreatic islets is very tightly coupled to changes in the blood glucose; abnormalities in insulin secretion are a major factor in both type 1 and type 2 diabetes. Our laboratory is conducting research in three areas. First, we are studying the sequence of molecular events and factors important for the development of normal islet vasculature. Pancreatic islets are extensively vascularized and this is important in their ability to sense the blood glucose and quickly secrete insulin. Second, we are investigating the molecular mechanisms of islet growth and regeneration with a focus on growth factors and signal transduction pathways in both rodent and human pancreatic islets. We have developed a new model where beta cell proliferation is related to islet cell interactions with macrophages and endothelial cells. Third, we are developing in vivo bioluminescence and other technologies to image and quantify pancreatic islets in vivo. Many of our studies involve the study of the human pancreas or human islets transplanted into immunodeficient mice to generate information relevant to human diabetes. Our research utilizes research approaches such as RNA and protein analysis, genetically modified mice, in vivo physiology, radioimmunoassay, adenovirus mediated gene transfer, transplantation of murine and human islets, confocal microscopy, and immunocytochemistry and involves collaborations with vascular biologists, development biologists, biomedical engineers, and transplant biologists.