U.S. Department of Energy

Pacific Northwest National Laboratory

Characterization of the human pancreatic islet proteome by two-dimensional LC/MS/MS.

TitleCharacterization of the human pancreatic islet proteome by two-dimensional LC/MS/MS.
Publication TypeJournal Article
Year of Publication2006
AuthorsMetz TO, Jacobs JM, Gritsenko MA, Fontès G, Qian W-J, Camp DG, Poitout V, Smith RD
JournalJ Proteome Res
KeywordsChromatography, Liquid, Humans, Islets of Langerhans, Mass Spectrometry, Peptide Library, Peptides, Proteins, Proteomics, Signal Transduction
Abstract

The pancreatic beta-cell plays a central role in the maintenance of glucose homeostasis and in the pathogenesis of both type 1 and type 2 diabetes mellitus. Elucidation of the insulin secretory defects observed in diabetes first requires a better understanding of the complex mechanisms regulating insulin secretion, which are only partly understood. While there have been reports detailing proteomic analyses of 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 islet biology 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 confident identification of 29,021 different tryptic peptides covering 3365 proteins (> or =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 transcription factors. In addition, significant proteome coverage of metabolic enzymes and cellular pathways was observed, including the integrin signaling cascade and the MAP kinase, NF-kappa beta, and JAK/STAT pathways. The resulting peptide reference library provides a resource for future higher throughput and quantitative studies of islet biology.

DOI10.1021/pr060322n
Alternate JournalJ. Proteome Res.
PubMed ID17137336
PubMed Central IDPMC2975945
Grant ListP41 RR018522-04 / RR / NCRR NIH HHS / United States
R21 DK070146 / DK / NIDDK NIH HHS / United States
RR18522 / RR / NCRR NIH HHS / United States
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