Characterization of the Human Pancreatic Islet Proteome by Two-Dimensional LC/MS/MS

Journal Article · Fri Dec 01 00:00:00 EST 2006 · Journal of Proteome Research, 5(12):3345-3354

DOI:https://doi.org/10.1021/pr060322n· OSTI ID:897685

Metz, Thomas O; Jacobs, Jon M; Gritsenko, Marina A; Fontes, Ghislaine; Qian, Weijun; Camp, David G; Poitout, Vincent J; Smith, Richard D

Research to elucidate the pathogenesis of type 1 diabetes mellitus has traditionally focused on the genetic and immunological factors associated with the disease, and, until recently, has not considered the target cell. While there have been reports detailing proteomic analyses of established islet cell lines or isolated rodent islets, the information gained is not always easily extrapolated to humans. Therefore, extensive characterization of the human islet proteome could result in 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 detection of 29,021 unique peptides corresponding to 4,925 proteins. As expected, major islet hormones (insulin, glucagon, somatostatin), beta-cell enriched secretory products (IAPP), ion channels (K-ATP channel), and transcription factors (PDX-1, Nkx 6.1, HNF-1 beta) were detected. In addition, significant proteome coverage of metabolic enzymes and cellular pathways was obtained, including the insulin signaling cascade and the MAP kinase, NF-κβ, and JAK/STAT pathways. This work represents the most extensive characterization of the human islet proteome to date and provides a peptide reference library that may be utilized in future studies of islet biology and type 1 diabetes.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 897685
• Report Number(s): PNNL-SA-49730; 12500; 400412000; TRN: US200705%%290
• Journal Information: Journal of Proteome Research, 5(12):3345-3354, Journal Name: Journal of Proteome Research, 5(12):3345-3354
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BIOLOGY
DETECTION
DIABETES MELLITUS
ENZYMES
GENETICS
GLUCAGON
HORMONES
INSULIN
PATHOGENESIS
PEPTIDES
PROTEINS
RODENTS
SOMATOSTATIN
TARGETS
TRANSCRIPTION FACTORS
diabetes
human islets
proteomics
liquid chromatography
mass spectrometry
Environmental Molecular Sciences Laboratory