Localization of dipeptidyl peptidase-4 (CD26) to human pancreatic ducts and islet alpha cells

Diabetes Res Clin Pract. 2015 Dec;110(3):291-300. doi: 10.1016/j.diabres.2015.10.010. Epub 2015 Oct 26.

Abstract

Aim: 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.

Conclusion: 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.

Keywords: Alpha cell; Beta cell; CD26; Dipeptidyl peptidase-4; Human pancreas; Islet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Female
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Secreting Cells / metabolism*
  • Humans
  • Immunohistochemistry
  • Incretins / metabolism
  • Insulin-Secreting Cells / metabolism
  • Male
  • Middle Aged
  • Pancreatic Ducts / metabolism*
  • Proinsulin / metabolism
  • Young Adult

Substances

  • Incretins
  • Glucagon-Like Peptide 1
  • Glucagon
  • Proinsulin
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4