Islet Cell Biology
Islet cell therapy is a very promising treatment for type 1 diabetes, but suffers from variability in the cell preparations used for transplantation. As part of this clinical program, my group has developed several new approaches for islet cell characterization, including metabolic parameters and gene expression profiling for evaluation of the islet cells prior to transplantation. Glucose stimulates insulin secretion from islets, and we are quantifying this response by the oxygen consumption rate and changes in cytochrome reduction. We have shown that these parameters have a high correlation with the ability of islets to reverse diabetes, and therefore identify “good” islet preparations. In a parallel study, we completed the gene expression profiling of several islet preparations and have identified a “gene signature” of islet quality. This geneset accurately predicts in vivo efficacy of transplanted islets, and we are developing a diagnostic test for islet function. We are also exploring the functional roles of these genes, which should lead to a better understanding of islet biology and better treatments for diabetics.
Circulating Nucleic Acids
A major difficult in both islet transplantation therapy and in diabetes in general is the lack of diagnostic tests that can be used to monitor islets in vivo. Based on the hypothesis that dying islet cells release cell debris into circulation, my group is measuring specific nucleic acids in the blood of our islet recipients and new onset diabetic patients. We have developed a highly sensitive and specific method to detect DNA from transplanted islets in the recipient’s circulation and find that the levels correlate with damage to the islet grafts. Recently we developed a similar test based on a unique DNA pattern we discovered for early detection of type 1 diabetes. These early markers of islet injury will allow timely intervention to prevent further loss of islet cells. We are building on these approaches to develop biomarkers for type 2 diabetes and diabetic complications.
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