title: Localization of dipeptidyl peptidase-4 (CD26) to human pancreatic ducts and islet alpha cells.
abstract: OBJECTIVE
  DPP-4/CD26 degrades the incretins GLP-1 and GIP. The localization of DPP-4 within the human pancreas is not well documented but is likely to be relevant for understanding incretin function. We aimed to define the cellular localization of DPP-4 in the human pancreas from cadaveric organ donors with and without diabetes.
  
  
  METHODS
  Pancreas was snap-frozen and immunoreactive DPP-4 detected in cryosections using the APAAP technique. For co-localization studies, pancreas sections were double-stained for DPP-4 and proinsulin or glucagon and scanned by confocal microscopy. Pancreata were digested and cells in islets and in islet-depleted, duct-enriched digests analyzed for expression of DPP-4 and other markers by flow cytometry.
  
  
  RESULTS
  DPP-4 was expressed by pancreatic duct and islet cells. In pancreata from donors without diabetes or with type 2 diabetes, DPP-4-positive cells in islets had the same location and morphology as glucagon-positive cells, and the expression of DPP-4 and glucagon overlapped. In donors with type 1 diabetes, the majority of residual cells in islets were DPP-4-positive.
  
  
  CONCLUSIONS
  In the human pancreas, DPP-4 expression is localized to duct and alpha cells. This finding is consistent with the view that DPP-4 regulates exposure to incretins of duct cells directly and of beta cells indirectly in a paracrine manner.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia; The Institute of Diabetes "Gerhardt Katsch", 17440 Karlsburg, Greifswald, Germany. Electronic address: paugstein@diabetes-karlsburg.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Augstein
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: naselli@wehi.edu.au.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Naselli
authors.affiliation: St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia. Electronic address: tloudovaris@svi.edu.au.
authors.forename: Thomas
authors.initials: T
authors.lastname: Loudovaris
authors.affiliation: University of Sydney, Department of Surgery, Westmead Hospital, Westmead, NSW, Australia. Electronic address: wayne.hawthorne@sydney.edu.au.
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Hawthorne
authors.affiliation: St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Campbell
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: bandala@wehi.edu.au.
authors.forename: Esther
authors.initials: E
authors.lastname: Bandala-Sanchez
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: rogers@wehi.edu.au.
authors.forename: Kelly
authors.initials: K
authors.lastname: Rogers
authors.affiliation: The Institute of Diabetes "Gerhardt Katsch", 17440 Karlsburg, Greifswald, Germany. Electronic address: heinke@diabetes-karlsburg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Heinke
authors.affiliation: St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia. Electronic address: hthomas@svi.edu.au.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Thomas
authors.affiliation: St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia. Electronic address: tkay@svi.edu.au.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kay
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: harrison@wehi.edu.au.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D054795:Incretins / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010183:Pancreatic Ducts / Q000378:metabolism*; D011384:Proinsulin / Q000378:metabolism; D055815:Young Adult
chemical_list: D054795:Incretins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D011384:Proinsulin; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Alpha cell; Beta cell; CD26; Dipeptidyl peptidase-4; Human pancreas; Islet