Petra Augstein1, Gaetano Naselli2, Thomas Loudovaris3, Wayne J Hawthorne4, Peter Campbell5, Esther Bandala-Sanchez6, Kelly Rogers7, Peter Heinke8, Helen E Thomas9, Thomas W Kay10, Leonard C Harrison11. 1. 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. 2. Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: naselli@wehi.edu.au. 3. St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia. Electronic address: tloudovaris@svi.edu.au. 4. University of Sydney, Department of Surgery, Westmead Hospital, Westmead, NSW, Australia. Electronic address: wayne.hawthorne@sydney.edu.au. 5. St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia. 6. Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: bandala@wehi.edu.au. 7. Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: rogers@wehi.edu.au. 8. The Institute of Diabetes "Gerhardt Katsch", 17440 Karlsburg, Greifswald, Germany. Electronic address: heinke@diabetes-karlsburg.de. 9. St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia. Electronic address: hthomas@svi.edu.au. 10. St Vincent's Institute of Medical Research, 3056 Fitzroy, 41 Victoria Parade, Victoria, Australia. Electronic address: tkay@svi.edu.au. 11. Walter and Eliza Hall Institute of Medical Research, 3052 Parkville, 1G Royal Parade, Victoria, Australia. Electronic address: harrison@wehi.edu.au.
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.
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.
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