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.
- MeSH
- buňky vylučující glukagon enzymologie MeSH
- dipeptidylpeptidasa 4 analýza MeSH
- dospělí MeSH
- glukagon analýza MeSH
- imunohistochemie MeSH
- konfokální mikroskopie MeSH
- Langerhansovy ostrůvky cytologie enzymologie MeSH
- lidé MeSH
- membránové proteiny analýza MeSH
- serinové endopeptidasy analýza MeSH
- želatinasy analýza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- autoantigeny MeSH
- autoprotilátky analýza MeSH
- buněčná imunita MeSH
- coxsackie virózy imunologie komplikace MeSH
- diabetes mellitus 1. typu enzymologie imunologie patologie MeSH
- glutamát dekarboxyláza imunologie MeSH
- Langerhansovy ostrůvky enzymologie imunologie patologie MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH