Journal
JOURNAL OF PROTEOME RESEARCH
Volume 7, Issue 8, Pages 3114-3126Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr800205b
Keywords
LC-MS/MS; pancreatic islets; proteomics; diabetes; mouse model; mass spectrometry; interaction network
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Funding
- NCRR NIH HHS [P41 RR018522, P41 RR018522-06, RR 018522] Funding Source: Medline
- NIDDK NIH HHS [R01 DK067536, R01 DK074795, R01 DK 67536] Funding Source: Medline
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The pancreatic islets of Langerhans, and especially the insulin-producing beta cells, play a central role in the maintenance of glucose homeostasis. Alterations in the expression of multiple proteins in the islets that contribute to the maintenance of islet function are likely to underlie the pathogenesis of types 1 and 2 diabetes. To identify proteins that constitute the islet proteome, we provide the first comprehensive proteomic characterization of pancreatic islets for mouse, the most commonly used animal model in diabetes research. Using strong cation exchange fractionation coupled with reversed phase LC-MS/MS we report the confident identification of 17 350 different tryptic peptides covering 2612 proteins having at least two unique peptides per protein. The data set also identified similar to 60 post-translationally modified peptides including oxidative modifications and phosphorylation. While many of the identified phosphorylation sites corroborate those previously known, the oxidative modifications observed on cysteinyl residues reveal potentially novel information suggesting a role for oxidative stress in islet function. Comparative analysis with 15 available proteomic data sets from other mouse tissues and cells revealed a set of 133 proteins predominantly expressed in pancreatic islets. This unique set of proteins, in addition to those with known functions such as peptide hormones secreted from the islets, contains several proteins with as yet unknown functions. The mouse islet protein and peptide database accessible at http://ncrr.pnl.gov, provides an important reference resource for the research community to facilitate research in the diabetes and metabolism fields.
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