title: Co-expression of the homologous proteases fibroblast activation protein and dipeptidyl peptidase-IV in the adult human Langerhans islets.
abstract: Fibroblast activation protein (FAP, seprase, EC 3.4.21.B28) and dipeptidyl peptidase-IV (DPP-IV, CD26, EC 3.4.14.5) are homologous serine proteases implicated in the modulation of the bioavailability and thus the function of a number of biologically active peptides. In spite of their generally nonoverlapping expression patterns, DPP-IV and FAP are co-expressed and probably co-regulated in certain cell types suggesting that for some biological processes their functional synergy is essential. By an in situ enzymatic activity assay, we show an abundant DPP-IV-like enzymatic activity sensitive to a highly specific DPP-IV inhibitor sitagliptin and corresponding DPP-IV immunoreactivity in the adult human islets of Langerhans. Moreover, the homologous protease FAP was present in the human endocrine pancreas and was co-expressed with DPP-IV. DPP-IV and FAP were found in the pancreatic alpha cells as determined by the co-localization with glucagon immunoreactivity. In summary, we show abundant enzymatic activity of the canonical DPP-IV (CD26) in Langerhans islets in the natural tissue context and demonstrate for the first time the co-expression of FAP and DPP-IV in pancreatic alpha cells in adult humans. Given their ability to proteolytically modify several biologically active peptides, both proteases have the potential to modulate the paracrine signaling in the human Langerhans islets.
authors.affiliation: Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic, busekpetr@seznam.cz.
authors.forename: Petr
authors.initials: P
authors.lastname: Busek
authors.forename: Petr
authors.initials: P
authors.lastname: Hrabal
authors.forename: Premysl
authors.initials: P
authors.lastname: Fric
authors.forename: Aleksi
authors.initials: A
authors.lastname: Sedo
mesh_terms: D000328:Adult; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis*; D010450:Endopeptidases; D018093:Gelatinases / Q000032:analysis*; D005934:Glucagon / Q000032:analysis; D050416:Glucagon-Secreting Cells / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology / Q000201:enzymology*; D008565:Membrane Proteins / Q000032:analysis*; D018613:Microscopy, Confocal; D012697:Serine Endopeptidases / Q000032:analysis*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D018819:Dipeptidyl Peptidase 4; D010450:Endopeptidases; D018093:Gelatinases; D005934:Glucagon; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C042807:DPP4 protein, human