The pancreatic beta-cell plays a central role in the maintenance of glucose homeostasis and in thepathogenesis of both type 1 and type 2 diabetes mellitus. Elucidation of the insulin secretory defectsobserved in diabetes first requires a better understanding of the complex mechanisms regulating insulinsecretion, which are only partly understood. While there have been reports detailing proteomic analysesof islet cell lines or isolated rodent islets, the information gained is not always applicable to humans.Therefore, definition of the human islet proteome could contribute to a better understanding of isletbiology and lead to more effective treatment strategies. We have applied a two-dimensional LC-MS/MS-based analysis to the characterization of the human islet proteome, resulting in the confidentidentification of 29 021 different tryptic peptides covering 3365 proteins (
2 unique peptide identifications per protein). As expected, the three major islet hormones (insulin, glucagon, and somatostatin)were detected, as well as various beta-cell enriched secretory products, ion channels, and transcriptionfactors. In addition, significant proteome coverage of metabolic enzymes and cellular pathways wasobserved, including the integrin signaling cascade and the MAP kinase, NF-
, and JAK/STAT pathways.The resulting peptide reference library provides a resource for future higher throughput and quantitativestudies of islet biology.