DPP4 in Diabetes
Dipeptidyl peptidase 4 (DPP4) is a glycoprotein of 110 kDa, which is ubiquitously expressed on the surface of a variety of cells. This exopeptidase selectively cleaves N-terminal dipeptides from a variety of substrates, including cytokines, growth factors neuropeptides, and the incretin hormones. Ex...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00386/full |
| _version_ | 1811318787457155072 |
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| author | Diana eRöhrborn Nina eWronkowitz Juergen eEckel |
| author_facet | Diana eRöhrborn Nina eWronkowitz Juergen eEckel |
| author_sort | Diana eRöhrborn |
| collection | DOAJ |
| description | Dipeptidyl peptidase 4 (DPP4) is a glycoprotein of 110 kDa, which is ubiquitously expressed on the surface of a variety of cells. This exopeptidase selectively cleaves N-terminal dipeptides from a variety of substrates, including cytokines, growth factors neuropeptides, and the incretin hormones. Expression of DPP4 is substantially dysregulated in a variety of disease states including inflammation, cancer, obesity and diabetes. Since the incretin hormones GLP-1 and GIP are major regulators of post-prandial insulin secretion, inhibition of DPP4 by the gliptin family of drugs has gained considerable interest for the therapy of type 2 diabetic patients. In this review, we summarise the current knowledge on the DPP4 - incretin axis, and evaluate most recent findings on DPP4 inhibitors.Furthermore, DPP4 as a type II transmembrane protein is also known to be cleaved from the cell membrane involving different metalloproteases in a cell-type specific manner. Circulating, soluble DPP4 has been identified as a new adipokine which exerts both para- and endocrine effects. Recently, a novel receptor for soluble DPP4 has been identified and data are accumulating that the adipokine-related effects of DPP4 may play an important role in the pathogenesis of cardiovascular disease. Importantly, circulating DPP4 is augmented in obese and type 2 diabetic subjects and it may represent a molecular link between obesity and vascular dysfunction. A critical evaluation of the impact of circulating DPP4 is presented and the potential role of DPP4 inhibition at this level is also discussed. |
| first_indexed | 2024-04-13T12:31:35Z |
| format | Article |
| id | doaj.art-3bcaa864c3e44e678ab8a39560c39b0c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T12:31:35Z |
| publishDate | 2015-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3bcaa864c3e44e678ab8a39560c39b0c2022-12-22T02:46:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-07-01610.3389/fimmu.2015.00386150851DPP4 in DiabetesDiana eRöhrborn0Nina eWronkowitz1Juergen eEckel2German Diabetes CenterGerman Diabetes CenterGerman Diabetes CenterDipeptidyl peptidase 4 (DPP4) is a glycoprotein of 110 kDa, which is ubiquitously expressed on the surface of a variety of cells. This exopeptidase selectively cleaves N-terminal dipeptides from a variety of substrates, including cytokines, growth factors neuropeptides, and the incretin hormones. Expression of DPP4 is substantially dysregulated in a variety of disease states including inflammation, cancer, obesity and diabetes. Since the incretin hormones GLP-1 and GIP are major regulators of post-prandial insulin secretion, inhibition of DPP4 by the gliptin family of drugs has gained considerable interest for the therapy of type 2 diabetic patients. In this review, we summarise the current knowledge on the DPP4 - incretin axis, and evaluate most recent findings on DPP4 inhibitors.Furthermore, DPP4 as a type II transmembrane protein is also known to be cleaved from the cell membrane involving different metalloproteases in a cell-type specific manner. Circulating, soluble DPP4 has been identified as a new adipokine which exerts both para- and endocrine effects. Recently, a novel receptor for soluble DPP4 has been identified and data are accumulating that the adipokine-related effects of DPP4 may play an important role in the pathogenesis of cardiovascular disease. Importantly, circulating DPP4 is augmented in obese and type 2 diabetic subjects and it may represent a molecular link between obesity and vascular dysfunction. A critical evaluation of the impact of circulating DPP4 is presented and the potential role of DPP4 inhibition at this level is also discussed.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00386/fullIncretinsmultifunctional enzymetype 2 diabetes mellitusCD26/DPP4soluble DPP4DPP4 inhibitors/Gliptins |
| spellingShingle | Diana eRöhrborn Nina eWronkowitz Juergen eEckel DPP4 in Diabetes Frontiers in Immunology Incretins multifunctional enzyme type 2 diabetes mellitus CD26/DPP4 soluble DPP4 DPP4 inhibitors/Gliptins |
| title | DPP4 in Diabetes |
| title_full | DPP4 in Diabetes |
| title_fullStr | DPP4 in Diabetes |
| title_full_unstemmed | DPP4 in Diabetes |
| title_short | DPP4 in Diabetes |
| title_sort | dpp4 in diabetes |
| topic | Incretins multifunctional enzyme type 2 diabetes mellitus CD26/DPP4 soluble DPP4 DPP4 inhibitors/Gliptins |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00386/full |
| work_keys_str_mv | AT dianaerohrborn dpp4indiabetes AT ninaewronkowitz dpp4indiabetes AT juergeneeckel dpp4indiabetes |