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

•In the human pancreas, DPP-4 expression is localized to duct and alpha cells.•In donors with type 1 diabetes, the majority of islet cells are DPP-4-positive.•In donors without diabetes, DPP-4 and proinsulin have a distinct expression.•In duct-enriched samples, the majority of DPP-4-positive cells express CD133.

AimDPP-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.MethodsPancreas 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.ResultsDPP-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.ConclusionIn 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.