dipeptidyl peptidase 4


Summary: A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation.

Top Publications

  1. Lee J, Wang T, Liu C, Chien M, Chen M, Hsu Y, et al. Dipeptidyl Peptidase IV as a Prognostic Marker and Therapeutic Target in Papillary Thyroid Carcinoma. J Clin Endocrinol Metab. 2017;102:2930-2940 pubmed publisher
    ..Increased DPP4 expression is associated with cellular invasion and more aggressive disease in papillary thyroid cancer. Targeting DPP4 may be a therapeutic strategy for DPP4-expressing thyroid cancer. ..
  2. Singer E, Shin D, Nattkemper L, Benoit B, Klein R, Didigu C, et al. IL-31 is produced by the malignant T-cell population in cutaneous T-Cell lymphoma and correlates with CTCL pruritus. J Invest Dermatol. 2013;133:2783-2785 pubmed publisher
  3. Böhm A, Wagner R, Machicao F, Holst J, Gallwitz B, Stefan N, et al. DPP4 gene variation affects GLP-1 secretion, insulin secretion, and glucose tolerance in humans with high body adiposity. PLoS ONE. 2017;12:e0181880 pubmed publisher
    ..Whether this SNP underlies the reported inter-individual variance in responsiveness to DPP-4 inhibitors, at least in subjects with high body fat content, remains to be shown. ..
  4. Kopinska A, Krawczyk Kuliś M, Dziaczkowska Suszek J, BIESZCZAD K, Jagoda K, Kyrcz Krzemien S. The importance of the number of transplanted cells with dipeptidyl peptidase-4 expression on the haematopoietic recovery and lymphocyte reconstitution in patients with multiple myeloma after autologous haematopoietic stem-cell transplantation. Hematol Oncol. 2017;35:225-231 pubmed publisher
    ..Copyright © 2015 John Wiley & Sons, Ltd. ..
  5. Ohara Nemoto Y, Nakasato M, Shimoyama Y, Baba T, Kobayakawa T, Ono T, et al. Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4. Infect Immun. 2017;85: pubmed publisher
    ..i>Porphyromonas gingivalis, a major pathogen of periodontitis, expresses dipeptidyl peptidase 4 (DPP4), which is involved in regulation of blood glucose levels by cleaving incretins in humans...
  6. Salaga M, Mokrowiecka A, Zielińska M, Malecka Panas E, Kordek R, Kamysz E, et al. New Peptide Inhibitor of Dipeptidyl Peptidase IV, EMDB-1 Extends the Half-Life of GLP-2 and Attenuates Colitis in Mice after Topical Administration. J Pharmacol Exp Ther. 2017;363:92-103 pubmed publisher
    ..Our results validate DPP IV as a pharmacological target for the anti-IBD drugs, and its inhibitors based on natural substrates, such as EMDB-1, have the potential to become valuable anti-inflammatory therapeutic agents. ..
  7. Bansho Y, Lee J, Nishida E, Nakajima Koyama M. Identification and characterization of secreted factors that are upregulated during somatic cell reprogramming. FEBS Lett. 2017;591:1584-1600 pubmed publisher
  8. Peck K, Scobey T, Swanstrom J, Jensen K, Burch C, Baric R, et al. Permissivity of Dipeptidyl Peptidase 4 Orthologs to Middle East Respiratory Syndrome Coronavirus Is Governed by Glycosylation and Other Complex Determinants. J Virol. 2017;91: pubmed publisher
    Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor...
  9. Nongonierma A, Lalmahomed M, Paolella S, FitzGerald R. Milk protein isolate (MPI) as a source of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides. Food Chem. 2017;231:202-211 pubmed publisher
    ..MPI hydrolysates may have potential for use as dietary ingredients with serum glucose lowering activity in humans. ..

More Information


  1. Suda M, Shimizu I, Yoshida Y, Hayashi Y, Ikegami R, Katsuumi G, et al. Inhibition of dipeptidyl peptidase-4 ameliorates cardiac ischemia and systolic dysfunction by up-regulating the FGF-2/EGR-1 pathway. PLoS ONE. 2017;12:e0182422 pubmed publisher
    b>Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined...
  2. Grujic M, Matić I, Crnogorac M, Velickovic A, Kolundžija B, Cordero O, et al. Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis. Clin Chem Lab Med. 2017;55:73-81 pubmed publisher
    ..Our results show that a decrease in DPPIV serum activity, but not CD26 expression, is present in an early stage of rheumatoid arthritis. ..
  3. Rea D, Van Elzen R, De Winter H, Van Goethem S, Landuyt B, Luyten W, et al. Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling. Eur J Med Chem. 2017;139:482-491 pubmed publisher
    ..Clinical isolates of P. gingivalis strains with high dipeptidyl peptidase 4 (DPP4) expression also had a high capacity for biofilm formation and were more infective...
  4. Kim K, Noh J, Bodogai M, Martindale J, Yang X, Indig F, et al. Identification of senescent cell surface targetable protein DPP4. Genes Dev. 2017;31:1529-1534 pubmed publisher
    ..Mass spectrometry analysis revealed that DPP4 (dipeptidyl peptidase 4) was selectively expressed on the surface of senescent, but not proliferating, human diploid fibroblasts...
  5. Real F, Xu M, Vila M, de Bolos C. Intestinal brush-border-associated enzymes: co-ordinated expression in colorectal cancer. Int J Cancer. 1992;51:173-81 pubmed
    ..In conclusion, expression of brush-border-associated enzymes occurs frequently in colorectal cancers and is regulated in a co-ordinated manner. These markers can be used for the phenotypic sub-classification of colorectal cancers. ..
  6. Brown S, Smith C, Meuth A, Khan M, Aroor A, Cleeton H, et al. Dipeptidyl Peptidase-4 Inhibition With Saxagliptin Ameliorates Angiotensin II-Induced Cardiac Diastolic Dysfunction in Male Mice. Endocrinology. 2017;158:3592-3604 pubmed publisher
    ..In summary, these results demonstrate that DPP-4 inhibition with Saxa prevents Ang II-induced cardiac diastolic dysfunction, fibrosis, and inflammation associated with unique shifts in CD11c-expressing leukocytes and CD8+ lymphocytes...
  7. Auger J, Chuzeville S, Roy D, Mathieu Denoncourt A, Xu J, Grenier D, et al. The bias of experimental design, including strain background, in the determination of critical Streptococcus suis serotype 2 virulence factors. PLoS ONE. 2017;12:e0181920 pubmed publisher
    ..Alongside, studies should include strains of diverse origins in order to prevent erroneous and biased conclusions that could affect future studies. ..
  8. Earnest J, Hantak M, Li K, McCray P, Perlman S, Gallagher T. The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases. PLoS Pathog. 2017;13:e1006546 pubmed publisher
    ..lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-..
  9. Huang C, Wang C, Lee Y, Peng C. Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced ? cell apoptosis via inhibiting dipeptidyl peptidase-4. PLoS ONE. 2017;12:e0180285 pubmed publisher
    ..In conclusion, AE is useful to prevent the exacerbation of ? cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes. ..
  10. Secrest M, Udell J, Filion K. The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors. Trends Cardiovasc Med. 2017;27:194-202 pubmed publisher
  11. Cuenco J, Minnion J, Tan T, Scott R, Germain N, Ling Y, et al. Degradation Paradigm of the Gut Hormone, Pancreatic Polypeptide, by Hepatic and Renal Peptidases. Endocrinology. 2017;158:1755-1765 pubmed publisher
    ..These findings suggest that inhibiting the degradation of PP using specific inhibitors and/or the design of analogs resistant to cleavage by DPPIV and NEP might be useful in the development of PP as an anti-obesity pharmacotherapy...
  12. Chen Z, Bao L, Chen C, Zou T, Xue Y, Li F, et al. Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset. J Infect Dis. 2017;215:1807-1815 pubmed publisher
    ..S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4)...
  13. Stieger B, Matter K, Baur B, Bucher K, Höchli M, Hauri H. Dissection of the asynchronous transport of intestinal microvillar hydrolases to the cell surface. J Cell Biol. 1988;106:1853-61 pubmed
    ..These results suggest that the observed asynchronism is due to more than one rate-limiting step along the rough endoplasmic reticulum to trans-Golgi pathway. ..
  14. Nauck M, Vilsbøll T, Gallwitz B, Garber A, Madsbad S. Incretin-based therapies: viewpoints on the way to consensus. Diabetes Care. 2009;32 Suppl 2:S223-31 pubmed publisher
  15. Akoumianakis I, Antoniades C. Dipeptidyl peptidase IV inhibitors as novel regulators of vascular disease. Vascul Pharmacol. 2017;96-98:1-4 pubmed publisher
    ..However, the exact pleiotropic mechanisms that underlie the cardiovascular effects of DPP-IV inhibition need to be clarified, while the in vivo benefit of DPP-IV inhibition in humans remains unclear. ..
  16. Kim Y, Yoon D, Park S, Han S, Kim D, Lee K, et al. Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study. Circ Heart Fail. 2017;10: pubmed publisher
    ..In addition, the risks for cardiovascular outcomes were not elevated in DPP-4i-treated patients compared with sulfonylurea-treated patients. ..
  17. Vanderheyden P, Benachour N. Influence of the cellular environment on ligand binding kinetics at membrane-bound targets. Bioorg Med Chem Lett. 2017;27:3621-3628 pubmed publisher
  18. Mah W, Jiang G, Olver D, Gallant Behm C, Wiebe C, Hart D, et al. Elevated CD26 Expression by Skin Fibroblasts Distinguishes a Profibrotic Phenotype Involved in Scar Formation Compared to Gingival Fibroblasts. Am J Pathol. 2017;187:1717-1735 pubmed publisher
    ..Thus, a CD26-positive fibroblast population that is abundant in human skin but not in gingiva may drive the profibrotic response leading to excessive scarring. ..
  19. Liu D, Gao H, Tang W, Nie S. Plant non-starch polysaccharides that inhibit key enzymes linked to type 2 diabetes mellitus. Ann N Y Acad Sci. 2017;1401:28-36 pubmed publisher
    ..In this short review we discuss published evidence for inhibition of these enzymes and the implications for treating T2DM. ..
  20. Sato A, Suzuki S, Watanabe S, Shimizu T, Nakamura Y, Misaka T, et al. DPP4 Inhibition Ameliorates Cardiac Function by Blocking the Cleavage of HMGB1 in Diabetic Mice After Myocardial Infarction. Int Heart J. 2017;58:778-786 pubmed publisher
    ..Although dipeptidyl peptidase 4 (DPP4) degrades certain peptides, it remains unclear as to whether HMGB1 is a substrate of DPP4 and ..
  21. Maezaki H, Tawada M, Yamashita T, Banno Y, Miyamoto Y, Yamamoto Y, et al. Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554. Bioorg Med Chem Lett. 2017;27:3565-3571 pubmed publisher
    ..The design strategy would be useful to explore a novel design for DPP-4 inhibitors having a distinct structure with a unique binding mode. ..
  22. Wang T, Hsieh C, Hung C, Jao C, Lin P, Hsieh Y, et al. A study to evaluate the potential of an in silico approach for predicting dipeptidyl peptidase-IV inhibitory activity in vitro of protein hydrolysates. Food Chem. 2017;234:431-438 pubmed publisher
    ..6993; P<0.05). Therefore, the in silico approach is effective to predict DPP-IV inhibitory activities in vitro of protein hydrolysates. ..
  23. Fernández Paredes L, Casrouge A, Decalf J, de Andrés C, Villar L, Pérez de Diego R, et al. Multimarker risk stratification approach at multiple sclerosis onset. Clin Immunol. 2017;181:43-50 pubmed publisher
  24. Fadini G, Bonora B, Albiero M, Zaninotto M, Plebani M, Avogaro A. DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes. Cardiovasc Diabetol. 2017;16:22 pubmed publisher
    ..As routinely used immunoassays do not discriminate between intact/active and cleaved BNP, these data cannot rule out an effect of DPP-4i on HF pathophysiology. Trial registration NCT01617824. ..
  25. Jiang S, Lu L, Du L, Debnath A. Putative conformations of the receptor-binding domain in S protein of hCoV-EMC in complex with its receptor dipeptidyl peptidase-4. J Infect. 2013;67:156-8 pubmed publisher
  26. Xin Y, Wang X, Zhu M, Qu M, Bogari M, Lin L, et al. Expansion of CD26 positive fibroblast population promotes keloid progression. Exp Cell Res. 2017;356:104-113 pubmed publisher
    ..Our findings suggest that CD26+ fibroblasts possess proliferation advantage in compare to CD26- fibroblasts, and the advantage caused expansion of CD26 positive fibroblast population promotes keloid progression. ..
  27. Han X, Qi J, Song H, Wang Q, Zhang Y, Wu Y, et al. Structure of the S1 subunit C-terminal domain from bat-derived coronavirus HKU5 spike protein. Virology. 2017;507:101-109 pubmed publisher
    ..Combined with sequence variation in the HKU5-CTD receptor binding interface, we propose the necessity for surveilling the mutation in BatCoV HKU5 spike protein in case of bat-to-human interspecies transmission. ..
  28. Nongonierma A, Hennemann M, Paolella S, Fitzgerald R. Generation of wheat gluten hydrolysates with dipeptidyl peptidase IV (DPP-IV) inhibitory properties. Food Funct. 2017;8:2249-2257 pubmed publisher
    ..The presence of Pro-containing peptides within H9 may contribute to its stability to digestive enzymes. Gluten hydrolysates may have antidiabetic potential for humans. ..
  29. Taga Y, Hayashida O, Kusubata M, Ogawa Goto K, Hattori S. Production of a novel wheat gluten hydrolysate containing dipeptidyl peptidase-IV inhibitory tripeptides using ginger protease. Biosci Biotechnol Biochem. 2017;81:1823-1828 pubmed publisher
    ..8, 70.9, 71.7, 56.7, and 78.9 ?M, respectively, suggesting that the novel gluten hydrolysate prepared using ginger protease can be used as a functional food for patients with type 2 diabetes. ..
  30. Zheng T, Chen B, Yang L, Hu X, Zhang X, Liu H, et al. Association of plasma dipeptidyl peptidase-4 activity with non-alcoholic fatty liver disease in nondiabetic Chinese population. Metabolism. 2017;73:125-134 pubmed publisher
    ..Plasma DPP4 activity is significantly associated with NAFLD. The underlying mechanisms may be partly attributed to the interactions between insulin resistance, oxidative stress, inflammation, and DPP4. ..
  31. Cordero O, Varela Calvino R, López González T, Grujic M, Juranic Z, Mouriño C, et al. Anti-CD26 autoantibodies are involved in rheumatoid arthritis and show potential clinical interest. Clin Biochem. 2017;50:903-910 pubmed publisher