"Adenosine receptors are expressed on immune cells and other tissues thought to regulate inflammatory events in mammals. Adenosine receptors, when activated by endogenous ligands or exogenous analogs, may repress inflammatory and immune pathways that lead to the destruction of pancreatic islets in models of type I diabetes and islet graft rejection. Building on our observations that inosine and NECA, two adenosine receptor agonists, inhibit diabetes and islet graft rejection in non-obese diabetic mice and multiple-low-dose-streptozotocin-treated mice, we postulate that certain adenosine receptor subtypes play a protective role in these type 1 diabetic mouse models. There are four types of adenosine receptors, all of which are members of the G protein-coupled family of receptors. The genes for these receptors have been analyzed in detail and they are designated A1, A2A, A2B, and A3. In this proposal we will attempt to delineate the exact roles for the various adenosine receptors in modulating the development of diabetes. By identifying which receptor(s) mediate the adenosine-mediated suppression of diabetes, we can utilize this information to develop new therapeutic approaches that specifically target the receptor(s) of interest."