title: Dipeptidyl peptidase-4 (DPP-4): Localization and activity in human and rodent islets.
abstract: Dipeptidyl peptidase 4 (DPP-4) was recently found to be expressed in human and mouse islets with different expression patterns. However, whether species-dependent expression pattern is a generalized phenomenon and whether islet DPP-4 activity is regulated are not known. This study was conducted to investigate DPP-4 localization in several different species, and to examine the impact of glucose, incretin hormones, and insulin on islet DPP-4 activity. It was shown by immuofluorescent staining that there were two distinct species-specific expression patterns of islet DPP-4. The enzyme was expressed exclusively in α-cells in human and pig islets, but primarily in β-cells in mouse and rat islets. INS-1 832/13 cells also expressed DPP-4, and inhibition of DPP-4 enhanced insulin secretion in the presence of glucagon-like peptide-1 (GLP-1) in the cells. DPP-4 activity was remarkably robust when cultured with high glucose, incretin hormones, and insulin in mouse and human islets as well as INS-1 832/13 cells and islet DPP-4 activity and expression pattern was not altered in double incretin receptor knockout mice, compared to wild type mice. We conclude that islet DPP-4 is species-specifically expressed in α-cell and β-cell dominant patterns in several species and both patterns remained robust in enzyme activity during short-term metabolic challenge.
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Clinical Sciences, Lund, Medicine, Lund University, SE22184 Lund, Sweden.
authors.forename: Liehua
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Clinical Sciences, Lund, Medicine, Lund University, SE22184 Lund, Sweden.
authors.forename: Bilal
authors.initials: B
authors.lastname: Omar
authors.affiliation: Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56126 Pisa, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Department of Clinical Sciences, Lund, Medicine, Lund University, SE22184 Lund, Sweden. Electronic address: bo.ahren@med.lu.se.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats
chemical_list: D007328:Insulin; D018819:Dipeptidyl Peptidase 4
keywords: Dipeptidyl peptidase 4; Incretin; Islet of Langerhans; Type 2 diabetes