title: Novel pancreatic beta cell-specific proteins: antibody-based proteomics for identification of new biomarker candidates.
abstract: Beta cell-specific surface targets are required for non-invasive monitoring of beta cell mass, which could be used for evaluation of new diabetes treatments as well as to help unravel pathogenic mechanisms underlying beta cell dysfunction. By antibody-based proteomics, we have identified and explored a set of islet cell-specific proteins. A search algorithm in the Human Protein Atlas was set up for identification of islet-specific proteins that yielded 27 hits, of which twelve showed a clear membranous expression pattern or had predicted transmembrane regions. The specificity of the identified proteins was investigated by immunohistochemical staining of pancreas sections from diabetic and non-diabetic subjects. No expression of these antigens could be detected in the exocrine pancreas. Colocalization with insulin and glucagon was further determined by confocal microscopy using isolated human islets. All antibodies specifically stained human islets and colocalization analysis revealed that four proteins were exclusively expressed in beta cells. Importantly, these antibodies were negative in sections from subjects with long-standing type 1 diabetes. In the present study, we present four proteins; DGCR2, GBF1, GPR44 and SerpinB10, the expression of which has not previously been described in beta cells.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindskog
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Jan W
authors.initials: JW
authors.lastname: Eriksson
authors.forename: Lars
authors.initials: L
authors.lastname: Johansson
authors.forename: Angelika
authors.initials: A
authors.lastname: Danielsson
mesh_terms: D000906:Antibodies / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D030562:Databases, Protein; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D019038:Platelet Glycoprotein GPIb-IX Complex; D040901:Proteomics; D011971:Receptors, Immunologic / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015415:Biomarkers; C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C096854:SERPINB10 protein, human; D015843:Serpins; C094990:adhesion receptor; D005934:Glucagon; C036293:prostaglandin D2 receptor