The goal of this project is to comprehensively profile the proteins expressed in human pancreas within both the islets and their surrounding environments, and to obtain relative expression levels of pancreatic proteins from different organ donor groups using mass spectrometry based bottom-up and top-down proteomics technologies. Snap-frozen pancreatic tissue sections from organ donor groups with 1) autoantibody negative, no diabetes; 2) autoantibody positive, no diabetes; 3) autoantibody positive and T1D; and 4) autoantibody negative and T2D will be analyzed on both the peptide and intact protein levels for comprehensive identification and quantification of proteins and protein isoforms that differentially expressed among these subject groups. To complement with our study on pancreatic tissue sections, islets and beta cells will be isolated from pancreatic tissues using laser capture microdissection for their comprehensive proteomic characterization and comparison as well. The significantly changed proteins and the specific pathways and networks they are involved in may serve as candidate biomarkers for diagnosis and aid in elucidation of the pathogenesis of T1D.