Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors

Endocrine Reviews

Volumn 35, Issue 6, 2014, Pages 992-1019

  Mulvihill, Erin E ^a   Drucker, Daniel J ^a  

^a MOUNT SINAI HOSPITAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN NATRIURETIC PEPTIDE; CHEMOKINE; CHEMOKINE CCL3L1; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EOTAXIN; ERYTHROPOIETIN; GASTRIC INHIBITORY POLYPEPTIDE; GASTRIN RELEASING PEPTIDE; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 2; GLUCOSE; GRANULOCYTE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GROWTH HORMONE RELEASING FACTOR; HIGH MOBILITY GROUP B1 PROTEIN; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; MACROPHAGE DERIVED CHEMOKINE; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; NEUROPEPTIDE Y; OXYNTOMODULIN; PEPTIDE YY; RANTES; SOMATOMEDIN C; STROMAL CELL DERIVED FACTOR 1; SUBSTANCE P; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; DRUG MECHANISM; DRUG SELECTIVITY; ENZYME ACTIVITY; EXPERIMENTAL MODEL; GENOMICS; HUMAN; MOLECULAR BIOLOGY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOPHYSIOLOGY; PHENOTYPE; PROTEIN EXPRESSION; REVIEW; T LYMPHOCYTE; ANIMAL; CLINICAL TRIAL (TOPIC); DIABETES MELLITUS, TYPE 2; DISEASE MODEL; DRUG EFFECTS; METABOLISM; MOUSE; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL PEPTIDASE 4; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DISEASE MODELS, ANIMAL; HUMANS; MICE; SIGNAL TRANSDUCTION;

EID: 84920095184     PISSN: None     EISSN: 0163769X     Source Type: Journal    
DOI: 10.1210/er.2014-1035     Document Type: Review

References (226)

1. Lambeir AM, Durinx C, Scharpé S, De Meester I. Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 2003;40:209-294.
2. Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C. Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science. 1993;261:466-469.
3. López-Otín C, Matrisian LM. Emerging roles of proteases in tumour suppression. Nat Rev Cancer. 2007;7:800-808.
4. Lu G, Hu Y, Wang Q, et al. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature. 2013;500:227-231.
5. Kahne T, Lendeckel U, Wrenger S, Neubert K, Ansorge S, Reinhold D. Dipeptidyl peptidase IV: a cell surface peptidase involved in regulating T cell growth (review). Int J Mol Med. 1999;4:3-15.
6. Davidson JA. The placement of DPP-4 inhibitors in clinical practice recommendations for the treatment of type 2 diabetes. Endocr Pract. 2013;19:1050-1061.
7. Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother. 2013;14:2047-2058.
8. Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev. 2012;33:187-215.
9. Solun B, Marcoviciu D, Dicker D. Dipeptidyl peptidase-4 inhibitors and their effects on the cardiovascular system. Curr Cardiol Rep. 2013;15:382.
10. Scheen AJ. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes. Postgrad Med. 2013;125:7-20.
11. Ramirez G, Morrison AD, Bittle PA. Clinical practice considerations and review of the literature for the use of DPP-4 inhibitors in patients with type 2 diabetes and chronic kidney disease. Endocr Pract. 2013;19:1025-1034.
12. Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs-FDA and EMA assessment. N Engl J Med. 2014;370:794-797.
13. Hopsu-Havu VK, Glenner GG. A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-β-naphthylamide. Histochemie. 1966;7:197-201.
14. McCaughan GW, Wickson JE, Creswick PF, Gorrell MD. Identification of the bile canalicular cell surface molecule GP110 as the ectopeptidase dipeptidyl peptidase IV: an analysis by tissue distribution, purification and N-terminal amino acid sequence. Hepatology. 1990;11:534-544.
15. Ulmer AJ, Mattern T, Feller AC, Heymann E, Flad HD. CD26 antigen is a surface dipeptidyl peptidase IV (DPPIV) as characterized by monoclonal antibodies clone TII-19-4-7 and 4EL1C7. Scand J Immunol. 1990;31:429-435.
16. Vivier I, Marguet D, Naquet P, et al. Evidence that thymocyte-activating molecule is mouse CD26 (dipeptidyl peptidase IV). J Immunol. 1991;147:447-454.
17. Misumi Y, Hayashi Y, Arakawa F, Ikehara Y. Molecular cloning and sequence analysis of human dipeptidyl peptidase IV, a serine proteinase on the cell surface. Biochim Biophys Acta. 1992;1131:333-336.
18. Tanaka T, Camerini D, Seed B, et al. Cloning and functional expression of the T cell activation antigen CD26. J Immunol. 1992;149:481-486.
19. Abbott CA, Baker E, Sutherland GR, McCaughan GW. Genomic organization, exact localization, and tissue expression of the human CD26 (dipeptidyl peptidase IV) gene. Immunogenetics. 1994;40:331-338.
20. Bernard AM, Mattei MG, Pierres M, Marguet D. Structure of the mouse dipeptidyl peptidase IV (CD26) gene. Biochemistry. 1994;33:15204-15214.
21. Fukasawa KM, Fukasawa K, Sahara N, Harada M, Kondo Y, Nagatsu I. Immunohistochemical localization of dipeptidyl aminopeptidase IV in rat kidney, liver, and salivary glands. J Histochem Cytochem. 1981;29:337-343.
22. Deacon CF. What do we know about the secretion and degradation of incretin hormones? Regul Pept. 2005;128:117-124.
23. Engel M, Hoffmann T, Wagner L, et al. The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism. Proc Natl Acad Sci USA. 2003;100:5063-5068.
24. Busek P, Malík R, Sedo A. Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer. Int J Biochem Cell Biol. 2004;36:408-421.
25. Hiramatsu H, Kyono K, Shima H, et al. Crystallization and preliminary x-ray study of human dipeptidyl peptidase IV (DPPIV). Acta Crystallogr D Biol Crystallogr. 2003;59:595-596.
26. Rasmussen HB, Branner S, Wiberg FC, Wagtmann N. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog. Nat Struct Biol. 2003;10:19-25.
27. Chien CH, Huang LH, Chou CY, et al. One site mutation disrupts dimer formation in human DPP-IV proteins. J Biol Chem. 2004;279:52338-52345.
28. Chien CH, Tsai CH, Lin CH, Chou CY, Chen X. Identification of hydrophobic residues critical for DPP-IV dimerization. Biochemistry. 2006;45:7006-7012.
29. Scanlan MJ, Raj BK, Calvo B, et al. Molecular cloning of fibroblast activation protein α, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA. 1994;91:5657-5661.
30. Ghersi G, Dong H, Goldstein LA, et al. Seprase-dPPIV association and prolyl peptidase and gelatinase activities of the protease complex. Adv Exp Med Biol. 2003;524:87-94.
31. Ohnuma K, Yamochi T, Uchiyama M, et al. CD26 upregulates expression of CD86 on antigen-presenting cells by means of caveolin-1. Proc Natl Acad Sci USA. 2004;101:14186-14191.
32. Ohnuma K, Uchiyama M, Yamochi T, et al. Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J Biol Chem. 2007;282:10117-10131.
33. Torimoto Y, Dang NH, Vivier E, Tanaka T, Schlossman SF, Morimoto C. Coassociation of CD26 (dipeptidyl peptidase IV) with CD45 on the surface of human T lymphocytes. J Immunol. 1991;147:2514-2517.
34. De Meester I, Korom S, Van Damme J, Scharpé S. CD26, let it cut or cut it down. Immunol Today. 1999;20:367-375.
35. Durinx C, Lambeir AM, Bosmans E, et al. Molecular characterization of dipeptidyl peptidase activity in serum: soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides. Eur J Biochem. 2000;267:5608-5613.
36. Nagatsu I, Nagatsu T, Yamamoto T. Hydrolysis of amino acid β-naphthylamides by aminopeptidases in human parotid salva and human serum. Experientia. 1968;24:347-348.
37. Cordero OJ, Salgado FJ, Nogueira M. On the origin of serum CD26 and its altered concentration in cancer patients. Cancer Immunol Immunother. 2009;58:1723-1747.
38. Yu DM, Slaitini L, Gysbers V, et al. Soluble CD26/dipeptidyl peptidase IV enhances human lymphocyte proliferation in vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding. Scand J Immunol. 2011;73:102-111.
39. Lamers D, Famulla S, Wronkowitz N, et al. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes. 2011;60:1917-1925.
40. Ohnuma K, Munakata Y, Ishii T, et al. Soluble CD26/dipeptidyl peptidase IV induces T cell proliferation through CD86 up-regulation on APCs. J Immunol. 2001;167:6745-6755.
41. Ikushima H, Munakata Y, Iwata S, et al. Soluble CD26/dipeptidyl peptidase IV enhances transendothelial migration via its interaction with mannose 6-phosphate/insulinlike growth factor II receptor. Cell Immunol. 2002;215:106-110.
42. Zhong J, Rao X, Rajagopalan S. An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. Atherosclerosis. 2013;226:305-314.
43. Erickson RH, Gum JR, Lotterman CD, Hicks JW, Lai RS, Kim YS. Regulation of the gene for human dipeptidyl peptidase IV by hepatocyte nuclear factor 1 α. Biochem J. 1999;338:91-97.
44. Qvist H, Sjöström H, Norén O. The TATA-less, GC-rich porcine dipeptidylpeptidase IV (DPPIV) promoter shows bidirectional activity. Biol Chem. 1998;379:75-81.
45. Böhm SK, Gum JR Jr, Erickson RH, Hicks JW, Kim YS. Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter. Biochem J. 1995;311:835-843.
46. Bauvois B, Djavaheri-Mergny M, Rouillard D, Dumont J, Wietzerbin J. Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells. Oncogene. 2000;19:265-272.
47. Mattern T, Reich C, Duchrow M, Ansorge S, Ulmer AJ, Flad HD. Antibody-induced modulation of CD26 surface expression. Immunology. 1995;84:595-600.
48. Cordero OJ, Salgado FJ, Viñuela JE, Nogueira M. Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes. Immunobiology. 1997;197:522-533.
49. Sell H, Blüher M, Klöting N, et al. Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro. Diabetes Care. 2013;36:4083-4090.
50. Wang Z, Grigo C, Steinbeck J, von Hörsten S, Amann K, Daniel C. Soluble DPP4 originates in part from bone marrow cells and not from the kidney. Peptides. 2014;57:109-117.
51. Fan H, Meng W, Kilian C, Grams S, Reutter W. Domainspecific N-glycosylation of the membrane glycoprotein dipeptidylpeptidase IV (CD26) influences its subcellular trafficking, biological stability, enzyme activity and protein folding. Eur J Biochem. 1997;246:243-251.
52. Marguet D, Baggio L, Kobayashi T, et al. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA. 2000;97:6874-6879.
53. Aertgeerts K, Ye S, Shi L, et al. N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme activity, homodimer formation, and adenosine deaminase binding. Protein Sci. 2004;13:145-154.
54. Delacour D, Gouyer V, Leteurtre E, et al. 1-Benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside blocks the apical biosynthetic pathway in polarized HT-29 cells. J Biol Chem. 2003;278:37799-37809.
55. Yamashita K, Tachibana Y, Matsuda Y, Katunuma N, Kochibe N, Kobata A. Comparative studies of the sugar chains of aminopeptidase N and dipeptidylpeptidase IV purified from rat kidney brush-border membrane. Biochemistry. 1988;27:5565-5573.
56. Smith RE, Talhouk JW, Brown EE, Edgar SE. The significance of hypersialylation of dipeptidyl peptidase IV (CD26) in the inhibition of its activity by Tat and other cationic peptides. CD26: a subverted adhesion molecule for HIV peptide binding. AIDS Res Hum Retroviruses. 1998;14:851-868.
57. Cuchacovich M, Gatica H, Pizzo SV, Gonzalez-Gronow M. Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoantibodies in patients with rheumatoid arthritis and other autoimmune diseases. Clin Exp Rheumatol. 2001;19:673-680.
58. Tiruppathi C, Miyamoto Y, Ganapathy V, Leibach FH. Genetic evidence for role of DPP IV in intestinal hydrolysis and assimilation of prolyl peptides. Am J Physiol. 1993; 265:G81-G89.
59. Brandt I, Lambeir AM, Ketelslegers JM, Vanderheyden M, Scharpé S, De Meester I. Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form. Clin Chem. 2006;52:82-87.
60. Niederkofler EE, Kiernan UA, O'Rear J, et al. Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure. Circ Heart Fail. 2008;1:258-264.
61. Boerrigter G, Costello-Boerrigter LC, Harty GJ, Lapp H, Burnett JC Jr. Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation. Am J Physiol Regul Integr Comp Physiol. 2007;292:R897-R901.
62. Gomez N, Touihri K, Matheeussen V, et al. Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing-induced heart failure. Eur J Heart Fail. 2012;14:14-21.
63. Broxmeyer HE, Hoggatt J, O'Leary HA, et al. Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis. Nat Med. 2012;18:1786-1796.
64. Struyf S, Proost P, Schols D, et al. CD26/dipeptidyl-peptidase IV down-regulates the eosinophil chemotactic potency, but not the anti-HIV activity of human eotaxin by affecting its interaction with CC chemokine receptor 3. J Immunol. 1999;162:4903-4909.
65. Spindel ER, Giladi E, Segerson TP, Nagalla S. Bombesinlike peptides: of ligands and receptors. Recent Prog Horm Res. 1993;48:365-391.
66. Lambeir AM, Durinx C, Proost P, Van Damme J, Scharpé S, De Meester I. Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion. FEBS Lett. 2001;507:327-330.
67. Ahrén B, Hughes TE. Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice. Endocrinology. 2005;146:2055-2059.
68. Roberge JN, Gronau KA, Brubaker PL. Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut. Endocrinology. 1996;137:2383-2388.
69. Reeve JR Jr, Walsh JH, Chew P, Clark B, Hawke D, Shively JE. Amino acid sequences of three bombesin-like peptides from canine intestine extracts. J Biol Chem. 1983;258:5582-5588.
70. Pospisilik JA, Hinke SA, Pederson RA, et al. Metabolism of glucagon by dipeptidyl peptidase IV (CD26). Regul Pept. 2001;96:133-141.
71. Deacon CF, Kelstrup M, Trebbien R, Klarskov L, Olesen M, Holst JJ. Differential regional metabolism of glucagon in anesthetized pigs. Am J Physiol Endocrinol Metab. 2003;285:E552-E560.
72. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab. 1995;80:952-957.
73. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17:819-837.
74. Knudsen LB, Pridal L. Glucagon-like peptide-1-(9-36) amide is a major metabolite of glucagon-like peptide-1-(7-36) amide after in vivo administration to dogs, and it acts as an antagonist on the pancreatic receptor. Eur J Pharmacol. 1996;318:429-435.
75. Nagakura T, Yasuda N, Yamazaki K, et al. Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats. Biochem Biophys Res Commun. 2001;284:501-506.
76. Meier JJ, Gethmann A, Nauck MA, et al. The glucagon-like peptide-1 metabolite GLP-1-(9-36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans. Am J Physiol Endocrinol Metab. 2006;290:E1118-E1123.
77. Elahi D, Egan JM, Shannon RP, et al. GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide. Obesity (Silver Spring). 2008;16:1501-1509.
78. Abu-Hamdah R, Rabiee A, Meneilly GS, Shannon RP, Andersen DK, Elahi D. Clinical review: the extrapancreatic effects of glucagon-like peptide-1 and related peptides. J Clin Endocrinol Metab. 2009;94:1843-1852.
79. Drucker DJ, Erlich P, Asa SL, Brubaker PL. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA. 1996;93:7911-7916.
80. Brubaker PL, Crivici A, Izzo A, Ehrlich P, Tsai CH, Drucker DJ. Circulating and tissue forms of the intestinal growth factor, glucagon-like peptide-2. Endocrinology. 1997;138:4837-4843.
81. Hartmann B, Harr MB, Jeppesen PB, et al. In vivo and in vitro degradation of glucagon-like peptide-2 in humans. J Clin Endocrinol Metab. 2000;85:2884-2888.
82. Shin ED, Estall JL, Izzo A, Drucker DJ, Brubaker PL. Mucosal adaptation to enteral nutrients is dependent on the physiologic actions of glucagon-like peptide-2 in mice. Gastroenterology. 2005;128:1340-1353.
83. Thulesen J, Knudsen LB, Hartmann B, et al. The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regul Pept. 2002;103:9-15.
84. Drucker DJ, Shi Q, Crivici A, et al. Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV. Nat Biotechnol. 1997;15:673-677.
85. Drucker DJ, Yusta B. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annu Rev Physiol. 2014;76:561-583.
86. Okawada M, Holst JJ, Teitelbaum DH. Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome. Surgery. 2011;150:217-223.
87. Hansen L, Hare KJ, Hartmann B, et al. Metabolism of glucagon-like peptide-2 in pigs: role of dipeptidyl peptidase IV. Regul Pept. 2007;138:126-132.
88. Hartmann B, Thulesen J, Kissow H, et al. Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice. Endocrinology. 2000;141:4013-4020.
89. Fujita Y, Wideman RD, Asadi A, et al. Glucose-dependent insulinotropic polypeptide is expressed in pancreatic islet α-cells and promotes insulin secretion. Gastroenterology. 2010;138:1966-1975.
90. Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology. 1995;136:3585-3596.
91. Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993;214:829-835.
92. Deacon CF, Nauck MA, Meier J, Hücking K, Holst JJ. Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab. 2000;85:3575-3581.
93. Deacon CF, Plamboeck A, Rosenkilde MM, de Heer J, Holst JJ. GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations. Am J Physiol Endocrinol Metab. 2006;291:E468-E475.
94. Gault VA, Parker JC, Harriott P, Flatt PR, O'Harte FP. Evidence that the major degradation product of glucosedependent insulinotropic polypeptide, GIP(3-42), is a GIP receptor antagonist in vivo. J Endocrinol. 2002;175:525-533.
95. Deacon CF, Wamberg S, Bie P, Hughes TE, Holst JJ. Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs. J Endocrinol. 2002;172:355-362.
96. Herman GA, Bergman A, Stevens C, et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab. 2006;91:4612-4619.
97. Hamilton JA, Achuthan A. Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol. 2013;34:81-89.
98. Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YC, Felix AM. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. J Clin Invest. 1986;78:906-913.
99. Frohman LA, Downs TR, Heimer EP, Felix AM. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. J Clin Invest. 1989;83:1533-1540.
100. Lin CT, Tang HY, Han YS, et al. Downregulation of signaling-active IGF-1 by dipeptidyl peptidase IV (DPP-IV). Int J Biomed Sci. 2010;6:301-309.
101. Faidley TD, Leiting B, Pryor KD, Lyons K, Hickey GJ, Thompson DR. Inhibition of dipeptidyl-peptidase IV does not increase circulating IGF-1 concentrations in growing pigs. Exp Biol Med (Maywood). 2006;231:1373-1378.
102. Bergman AJ, Stevens C, Zhou Y, et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a doubleblind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther. 2006;28:55-72.
103. Marchetti C, Di Carlo A, Facchiano F, et al. High mobility group box 1 is a novel substrate of dipeptidyl peptidase-IV. Diabetologia. 2012;55:236-244.
104. Proost P, Struyf S, Schols D, et al. Truncation of macrophage-derived chemokine by CD26/dipeptidyl-peptidase IV beyond its predicted cleavage site affects chemotactic activity and CC chemokine receptor 4 interaction. J Biol Chem. 1999;274:3988-3993.
105. Struyf S, Proost P, Sozzani S, et al. Enhanced anti-HIV-1 activity and altered chemotactic potency of NH2-terminally processed macrophage-derived chemokine (MDC) imply an additional MDC receptor. J Immunol. 1998;161:2672-2675.
106. Proost P, Menten P, Struyf S, Schutyser E, De Meester I, Van Damme J. Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78β into a most efficient monocyte attractant and CCR1 agonist. Blood. 2000;96:1674-1680.
107. Pocai A. Unraveling oxyntomodulin, GLP1's enigmatic brother. J Endocrinol. 2012;215:335-346.
108. Baggio LL, Huang Q, Brown TJ, Drucker DJ. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology. 2004;127:546-558.
109. Pocai A. Action and therapeutic potential of oxyntomodulin. Mol Metab. 2014;3:241-251.
110. Zhu L, Tamvakopoulos C, Xie D, et al. The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: in vivo metabolism of pituitary adenylate cyclase activating polypeptide-(1-38). J Biol Chem. 2003;278:22418-22423.
111. Bak MJ, Albrechtsen NW, Pedersen J, et al. Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in humans. Eur J Endocrinol. 2014;170:529-538.
112. Vaudry D, Falluel-Morel A, Bourgault S, et al. Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev. 2009;61:283-357.
113. Harmar AJ, Fahrenkrug J, Gozes I, et al. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol. 2012;166:4-17.
114. Yada T, Sakurada M, Ihida K, et al. Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet β-cells. J Biol Chem. 1994;269:1290-1293.
115. Jamen F, Persson K, Bertrand G, et al. PAC1 receptordeficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance. J Clin Invest. 2000;105:1307-1315.
116. Brothers SP, Wahlestedt C. Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Mol Med. 2010;2:429-439.
117. Frerker N, Wagner L, Wolf R, et al. Neuropeptide Y (NPY) cleaving enzymes: structural and functional homologues of dipeptidyl peptidase 4. Peptides. 2007;28:257-268.
118. Baticic L, Detel D, Kucic N, Buljevic S, Pugel EP, Varljen J. Neuroimmunomodulative properties of dipeptidyl peptidase IV/CD26 in a TNBS-induced model of colitis in mice. J Cell Biochem. 2011;112:3322-3333.
119. Mentlein R, Dahms P, Grandt D, Krüger R. Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV. Regul Pept. 1993;49:133-144.
120. Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002;418:650-654.
121. Unniappan S, McIntosh CH, Demuth HU, Heiser U, Wolf R, Kieffer TJ. Effects of dipeptidyl peptidase IV on the satiety actions of peptide YY. Diabetologia. 2006;49:1915-1923.
122. Aaboe K, Knop FK, Vilsbøll T, et al. Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and nonglucose induced insulin secretion in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2010;12:323-333.
123. Oravecz T, Pall M, Roderiquez G, et al. Regulation of the receptor specificity and function of the chemokine RAN-TES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage. J Exp Med. 1997;186:1865-1872.
124. Proost P, Schutyser E, Menten P, et al. Amino-terminal truncation of CXCR3 agonists impairs receptor signaling and lymphocyte chemotaxis, while preserving antiangiogenic properties. Blood. 2001;98:3554-3561.
125. Iwata S, Yamaguchi N, Munakata Y, et al. CD26/dipeptidyl peptidase IV differentially regulates the chemotaxis of T cells and monocytes toward RANTES: possible mechanism for the switch from innate to acquired immune response. Int Immunol. 1999;11:417-426.
126. Shirozu M, Nakano T, Inazawa J, et al. Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics. 1995;28:495-500.
127. Shioda T, Kato H, Ohnishi Y, et al. Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1α (SDF-1α) and SDF-1β are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage. Proc Natl Acad Sci USA. 1998;95:6331-6336.
128. Zaruba MM, Theiss HD, Vallaster M, et al. Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell. 2009;4:313-323.
129. Wang W, Choi BK, Li W, et al. Quantification of intact and truncated stromal cell-derived factor-1α in circulation by immunoaffinity enrichment and tandem mass spectrometry. J Am Soc Mass Spectrom. 2014;25:614-625.
130. Busso N, Wagtmann N, Herling C, et al. Circulating CD26 is negatively associated with inflammation in human and experimental arthritis. Am J Pathol. 2005;166:433-442.
131. Ahmad S, Wang L, Ward PE. Dipeptidyl(amino)peptidase IV and aminopeptidase M metabolize circulating substance P in vivo. J Pharmacol Exp Ther. 1992;260:1257-1261.
132. Guieu R, Fenouillet E, Devaux C, et al. CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity. Behav Brain Res. 2006;166:230-235.
133. Grouzmann E, Bigliardi P, Appenzeller M, Pannatier A, Buclin T. Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers. Biol Chem. 2011;392:217-221.
134. Cordero OJ, Salgado FJ, Mera-Varela A, Nogueira M. Serum interleukin-12, interleukin-15, soluble CD26, and adenosine deaminase in patients with rheumatoid arthritis. Rheumatol Int. 2001;21:69-74.
135. Hegen M, Mittrücker HW, Hug R, et al. Enzymatic activity of CD26 (dipeptidylpeptidase IV) is not required for its signalling function in T cells. Immunobiology. 1993;189:483-493.
136. Nemunaitis J, Vukelja SJ, Richards D, et al. Phase I trial of PT-100 (PT-100), a cytokine-inducing small molecule, following chemotherapy for solid tumor malignancy. Cancer Invest. 2006;24:553-561.
137. Eager RM, Cunningham CC, Senzer N, et al. Phase II trial of talabostat and docetaxel in advanced non-small cell lung cancer. Clin Oncol (R Coll Radiol). 2009;21:464-472.
138. Adams S, Miller GT, Jesson MI, Watanabe T, Jones B, Wallner BP. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004;64:5471-5480.
139. Nauck MA, Wollschläger D, Werner J, et al. Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM. Diabetologia. 1996;39:1546-1553.
140. Pauly RP, Rosche F, Wermann M, McIntosh CH, Pederson RA, Demuth HU. Investigation of glucose-dependent insulinotropic polypeptide-(1-42) and glucagon-like peptide-1-(7-36) degradation in vitro by dipeptidyl peptidase IV using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A novel kinetic approach. J Biol Chem. 1996;271:23222-23229.
141. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes. 1995;44:1126-1131.
142. Deacon CF, Hughes TE, Holst JJ. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagonlike peptide 1 in the anesthetized pig. Diabetes. 1998;47:764-769.
143. Pederson RA, White HA, Schlenzig D, Pauly RP, McIntosh CH, Demuth HU. Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide. Diabetes. 1998;47:1253-1258.
144. Balkan B, Kwasnik L, Miserendino R, Holst JJ, Li X. Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7-36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats. Diabetologia. 1999;42:1324-1331.
145. Karl T, Chwalisz WT, Wedekind D, et al. Localization, transmission, spontaneous mutations, and variation of function of the Dpp4 (dipeptidyl-peptidase IV; CD26) gene in rats. Regul Pept. 2003;115:81-90.
146. Tsuji E, Misumi Y, Fujiwara T, Takami N, Ogata S, Ikehara Y. An active-site mutation (Gly633->Arg) of dipeptidyl peptidase IV causes its retention and rapid degradation in the endoplasmic reticulum. Biochemistry. 1992;31:11921-11927.
147. Pederson RA, Kieffer TJ, Pauly R, Kofod H, Kwong J, McIntosh CH. The enteroinsular axis in dipeptidyl peptidase IV-negative rats. Metabolism. 1996;45:1335-1341.
148. Karl T, Hoffmann T, Pabst R, von Hörsten S. Extreme reduction of dipeptidyl peptidase IV activity in F344 rat substrains is associated with various behavioral differences. Physiol Behav. 2003;80:123-134.
149. Yasuda N, Nagakura T, Yamazaki K, Inoue T, Tanaka I. Improvement of high fat-diet-induced insulin resistance in dipeptidyl peptidase IV-deficient Fischer rats. Life Sci. 2002;71:227-238.
150. Kirino Y, Sato Y, Kamimoto T, Kawazoe K, Minakuchi K, Nakahori Y. Interrelationship of dipeptidyl peptidase IV (DPP4) with the development of diabetes, dyslipidaemia and nephropathy: a streptozotocin-induced model using wild-type and DPP4-deficient rats. J Endocrinol. 2009;200:53-61.
151. Conarello SL, Li Z, Ronan J, et al. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci USA. 2003;100:6825-6830.
152. Kirby M, Yu DM, O'Connor S, Gorrell MD. Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition. Clin Sci (Lond). 2010;118:31-41.
153. Thornberry NA, Weber AE. Discovery of JANUVIA (Sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Curr Top Med Chem. 2007;7:557-568.
154. Keane FM, Nadvi NA, Yao TW, Gorrell MD. Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are novel substrates of fibroblast activation protein-α. FEBS J. 2011;278:1316-1332.
155. Lankas GR, Leiting B, Roy RS, et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes. 2005;54:2988-2994.
156. Burkey BF, Hoffmann PK, Hassiepen U, Trappe J, Juedes M, Foley JE. Adverse effects of dipeptidyl peptidases 8 and 9 inhibition in rodents revisited. Diabetes Obes Metab. 2008;10:1057-1061.
157. Hoffmann P, Bentley P, Sahota P, et al. Vascular origin of vildagliptin-induced skin effects in cynomolgus monkeys: pathomechanistic role of peripheral sympathetic system and neuropeptide Y. Toxicol Pathol. 2014;42:684-695.
158. Bank U, Heimburg A, Wohlfarth A, et al. Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects. Biol Chem. 2011;392:169-187.
159. Gall MG, Chen Y, Vieira de Ribeiro AJ, et al. Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality. PLoS One. 2013;8: e78378.
160. Hung TT, Wu JY, Liu JF, Cheng HC. Epitope analysis of the rat dipeptidyl peptidase IV monoclonal antibody 6A3 that blocks pericellular fibronectin-mediated cancer cell adhesion. FEBS J. 2009;276:6548-6559.
161. Hanski C, Huhle T, Gossrau R, Reutter W. Direct evidence for the binding of rat liver DPP IV to collagen in vitro. Exp Cell Res. 1988;178:64-72.
162. Maida A, Hansotia T, Longuet C, Seino Y, Drucker DJ. Differential importance of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide 1 receptor signaling for β cell survival in mice. Gastroenterology. 2009;137:2146-2157.
163. Hansotia T, Baggio LL, Delmeire D, et al. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes. 2004;53:1326-1335.
164. Flock G, Baggio LL, Longuet C, Drucker DJ. Incretin receptors for glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide are essential for the sustained metabolic actions of vildagliptin in mice. Diabetes. 2007;56:3006-3013.
165. Hansen L, Deacon CF, Orskov C, Holst JJ. Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology. 1999;140:5356-5363.
166. Waget A, Cabou C, Masseboeuf M, et al. Physiological and pharmacological mechanisms through which the DPP-4 inhibitor sitagliptin regulates glycemia in mice. Endocrinology. 2011;152:3018-3029.
167. Lamont BJ, Li Y, Kwan E, Brown TJ, Gaisano H, Drucker DJ. Pancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice. J Clin Invest. 2012;122:388-402.
168. Ahrén B, Simonsson E, Larsson H, et al. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care. 2002;25:869-875.
169. Ahrén B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab. 2004;89:2078-2084.
170. Ahrén B, Gomis R, Standl E, Mills D, Schweizer A. Twelveand 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care. 2004;27:2874-2880.
171. Balas B, Baig MR, Watson C, et al. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after singledose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007;92:1249-1255.
172. Muscelli E, Casolaro A, Gastaldelli A, et al. Mechanisms for the antihyperglycemic effect of sitagliptin in patients with type 2 diabetes. J Clin Endocrinol Metab. 2012;97:2818-2826.
173. Solis-Herrera C, Triplitt C, Garduno-Garcia Jde J, Adams J, DeFronzo RA, Cersosimo E. Mechanisms of glucose lowering of dipeptidyl peptidase-4 inhibitor sitagliptin when used alone or with metformin in type 2 diabetes: a double-tracer study. Diabetes Care. 2013;36:2756-2762.
174. El-Ouaghlidi A, Rehring E, Holst JJ, et al. The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion. J Clin Endocrinol Metab. 2007;92:4165-4171.
175. Aulinger BA, Bedorf A, Kutscherauer G, et al. Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes. 2014;63:1079-1092.
176. Zhong J, Rao X, Deiuliis J, et al. A potential role for dendritic cell/macrophage-expressing DPP4 in obesity-induced visceral inflammation. Diabetes. 2013;62:149-157.
177. Bordicchia M, Liu D, Amri EZ, et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012;122:1022-1036.
178. Lockie SH, Heppner KM, Chaudhary N, et al. Direct control of brown adipose tissue thermogenesis by central nervous system glucagon-like peptide-1 receptor signaling. Diabetes. 2012;61:2753-2762.
179. Drucker DJ, Nauck MA. The incretin system: glucagonlike peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696-1705.
180. Matheeussen V, Waumans Y, Martinet W, et al. Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis. Basic Res Cardiol. 2013;108:350.
181. Shigeta T, Aoyama M, Bando YK, et al. Dipeptidyl peptidase-4 modulates left ventricular dysfunction in chronic heart failure via angiogenesis-dependent and -independent actions. Circulation. 2012;126:1838-1851.
182. Ussher JR, Drucker DJ. Cardiovascular actions of incretinbased therapies. Circ Res. 2014;114:1788-1803.
183. Sauvé M, Ban K, Momen MA, et al. Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice. Diabetes. 2010;59:1063-1073.
184. Ku HC, Chen WP, Su MJ. DPP4 deficiency preserves cardiac function via GLP-1 signaling in rats subjected to myocardial ischemia/reperfusion. Naunyn Schmiedebergs Arch Pharmacol. 2011;384:197-207.
185. Chang G, Zhang P, Ye L, et al. Protective effects of sitagliptin on myocardial injury and cardiac function in an ischemia/reperfusion rat model. Eur J Pharmacol. 2013;718:105-113.
186. Theiss HD, Vallaster M, Rischpler C, et al. Dual stem cell therapy after myocardial infarction acts specifically by enhanced homing via the SDF-1/CXCR4 axis. Stem Cell Res. 2011;7:244-255.
187. Christopherson KW, Cooper S, Hangoc G, Broxmeyer HE. CD26 is essential for normal G-CSF-induced progenitor cell mobilization as determined by CD26-/- mice. Exp Hematol. 2003;31:1126-1134.
188. Fadini GP, Albiero M, Seeger F, et al. Stem cell compartmentalization in diabetes and high cardiovascular risk reveals the role of DPP-4 in diabetic stem cell mobilopathy. Basic Res Cardiol. 2013;108:313.
189. Fadini GP, Boscaro E, Albiero M, et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1α. Diabetes Care. 2010;33:1607-1609.
190. Theiss HD, Gross L, Vallaster M, et al. Antidiabetic gliptins in combination with G-CSF enhances myocardial function and survival after acute myocardial infarction. Int J Cardiol. 2013;168:3359-3369.
191. Theiss HD, Brenner C, Engelmann MG, et al. Safety and efficacy of SITAgliptin plus GRanulocyte-colony-stimulating factor in patients suffering from Acute Myocardial Infarction (SITAGRAMI-Trial)-rationale, design and first interim analysis. Int J Cardiol. 2010;145:282-284.
192. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-1326.
193. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327-1335.
194. Bhatt DL, Cavender MA. Do dipeptidyl peptidase-4 inhibitors increase the risk of heart failure [published online June 25, 2014]? JACC Heart Fail. doi:10.1016/j.jchf.2014.05.005.
195. McMurray J. The vildagliptin in ventricular dysfunction diabetes trial (VIVIDD). In: Proceedings from the European Society of Cardiology; August 31-September 4, 2013; Amsterdam, The Netherlands.
196. Kröller-Schön S, Knorr M, Hausding M, et al. Glucoseindependent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition. Cardiovasc Res. 2012;96:140-149.
197. Nakamura K, Oe H, Kihara H, et al. DPP-4 inhibitor and α-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study. Cardiovasc Diabetol. 2014;13:110.
198. Ayaori M, Iwakami N, Uto-Kondo H, et al. Dipeptidyl peptidase-4 inhibitors attenuate endothelial function as evaluated by flow-mediated vasodilatation in type 2 diabetic patients. J Am Heart Assoc. 2013;2:e003277.
199. Rieg T, Gerasimova M, Murray F, et al. Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. Am J Physiol Renal Physiol. 2012; 303:F963-F971.
200. Hsieh J, Longuet C, Baker CL, et al. The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice. Diabetologia. 2010;53:552-561.
201. Matikainen N, Mänttäri S, Schweizer A, et al. Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes. Diabetologia. 2006;49:2049-2057.
202. Kojima Y, Kaga H, Hayashi S, et al. Comparison between sitagliptin and nateglinide on postprandial lipid levels: the STANDARD study. World J Diabetes. 2013;4:8-13.
203. Xiao C, Dash S, Morgantini C, Patterson BW, Lewis GF. Sitagliptin, a DPP-4 inhibitor, acutely inhibits intestinal lipoprotein particle secretion in healthy humans. Diabetes. 2014;63:2394-2401.
204. Yan S, Marguet D, Dobers J, Reutter W, Fan H. Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen. Eur J Immunol. 2003;33:1519-1527.
205. Vora KA, Porter G, Peng R, et al. Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses. BMC Immunol. 2009;10:19.
206. Yan S, Gessner R, Dietel C, Schmiedek U, Fan H. Enhanced ovalbumin-induced airway inflammation in CD26-/- mice. Eur J Immunol. 2012;42:533-540.
207. Ansarullah, Lu Y, Holstein M, DeRuyter B, Rabinovitch A, Guo Z. Stimulating β-cell regeneration by combining a GPR119 agonist with a DPP-IV inhibitor. PLoS One. 2013;8:e53345.
208. Kim SJ, Nian C, Doudet DJ, McIntosh CH. Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes. 2009;58:641-651.
209. Kim SJ, Nian C, McIntosh CH. Sitagliptin (MK0431) inhibition of dipeptidyl peptidase IV decreases nonobese diabetic mouse CD4+ T-cell migration through incretin-dependent and -independent pathways. Diabetes. 2010;59:1739-1750.
210. Makdissi A, Ghanim H, Vora M, et al. Sitagliptin exerts an antinflammatory action. J Clin Endocrinol Metab. 2012;97:3333-3341.
211. van Poppel PC, Gresnigt MS, Smits P, Netea MG, Tack CJ. The dipeptidyl peptidase-4 inhibitor vildagliptin does not affect ex vivo cytokine response and lymphocyte function in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2014;103:395-401.
212. Price JD, Linder G, Li WP, et al. Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study. Clin Exp Immunol. 2013;174:120-128.
213. Goodwin SR, Reeds DN, Royal M, Struthers H, Laciny E, Yarasheski KE. Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study. J Clin Endocrinol Metab. 2013;98:743-751.
214. Shirakawa J, Fujii H, Ohnuma K, et al. Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice. Diabetes. 2011;60:1246-1257.
215. Ben-Shlomo S, Zvibel I, Rabinowich L, et al. Dipeptidyl peptidase 4-deficient rats have improved bile secretory function in high fat diet-induced steatosis. Dig Dis Sci. 2013;58:172-178.
216. Panjwani N, Mulvihill EE, Longuet C, et al. GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE(-/-) mice. Endocrinology. 2013;154:127-139.
217. Stange T, Kettmann U, Holzhausen HJ. Immunoelectron microscopic single and double labelling of aminopeptidase N (CD 13) and dipeptidyl peptidase IV (CD 26). Acta Histochem. 1996;98:323-331.
218. Liu L, Liu J, Wong WT, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism. Hypertension. 2012;60:833-841.
219. von Websky K, Reichetzeder C, Hocher B. Physiology and pathophysiology of incretins in the kidney. Curr Opin Nephrol Hypertens. 2014;23:54-60.
220. Ceccarelli E, Guarino EG, Merlotti D, et al. Beyond glycemic control in diabetes mellitus: effects of incretin-based therapies on bone metabolism. Front Endocrinol (Lausanne). 2013;4:73.
221. Kyle KA, Willett TL, Baggio LL, Drucker DJ, Grynpas MD. Differential effects of PPAR-γ activation versus chemical or genetic reduction of DPP-4 activity on bone quality in mice. Endocrinology. 2011;152:457-467.
222. Bunck MC, Poelma M, EekhoffEM, et al. Effects of vildagliptin on postprandial markers of bone resorption and calcium homeostasis in recently diagnosed, well-controlled type 2 diabetes patients. J Diabetes. 2012;4:181-185.
223. Tinoco AD, Tagore DM, Saghatelian A. Expanding the dipeptidyl peptidase 4-regulated peptidome via an optimized peptidomics platform. J Am Chem Soc. 2010;132:3819-3830.
224. Tagore DM, Nolte WM, Neveu JM, et al. Peptidase substrates via global peptide profiling. Nat Chem Biol. 2009;5:23-25.
225. Tinoco AD, Kim YG, Tagore DM, et al. A peptidomics strategy to elucidate the proteolytic pathways that inactivate peptide hormones. Biochemistry. 2011;50:2213-2222.
226. Tammen H, Hess R, Rose H, Wienen W, Jost M. Peptidomic analysis of blood plasma after in vivo treatment with protease inhibitors-a proof of concept study. Peptides. 2008;29:2188-2195.