Dipeptidyl peptidase-4 inhibition: Linking chemical properties to clinical safety

Current Medicinal Chemistry

Volumn 18, Issue 31, 2011, Pages 4753-4760

  Matteucci, E ^a   Giampietro, O ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

Adverse effects; DPP4 inhibitors; Molecular mechanisms

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALOGLIPTIN; ALPHA GLUCOSIDASE INHIBITOR; CYTOKINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GLIMEPIRIDE; GLIPIZIDE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCOSE; HEMOGLOBIN A1C; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN; LINAGLIPTIN; MESSENGER RNA; METFORMIN; NEUROPEPTIDE; NEUROPEPTIDE Y; PIOGLITAZONE; PLACEBO; PRAMLINTIDE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; SULFONYLUREA DERIVATIVE; VASCULAR CELL ADHESION MOLECULE 1; VILDAGLIPTIN;

ACNE; ADD ON THERAPY; ALLERGY; ANEMIA; ANGIONEUROTIC EDEMA; AREA UNDER THE CURVE; ARTICLE; CARDIOTOXICITY; CELL SURVIVAL; CONSTIPATION; CONTACT DERMATITIS; DIARRHEA; DRUG ABSORPTION; DRUG ELIMINATION; DRUG ERUPTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; ENZYME INHIBITION; GASTROINTESTINAL SYMPTOM; GLUCOSE BLOOD LEVEL; HUMAN; HYPOGLYCEMIA; INFECTION; INSULIN RELEASE; INSULIN TREATMENT; IRON DEFICIENCY ANEMIA; LEUKOCYTE COUNT; LEUKOPENIA; LIFESTYLE MODIFICATION; LIPID METABOLISM; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PANCREATITIS; RHINOPHARYNGITIS; SIDE EFFECT; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION;

CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; GASTROINTESTINAL DISEASES; HUMANS; HYPOGLYCEMIC AGENTS; LIPID METABOLISM; PEPTIDYL-DIPEPTIDASE A; SUBSTRATE SPECIFICITY;

EID: 80054871921     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986711797535290     Document Type: Article

References (91)

1. American Diabetes Association: Standards of medical care in diabetes - 2011. Diabetes Care, 2011, 34, S11-61
2. Nathan, D.M.; Kuenen, J.; Borg, R.; Zheng, H.; Schoenfeld, D.; Heine, R.J.; A1c-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care, 2008, 31, 1473-1478
3. Action to Control Cardiovascular Risk in diabetes Study Group: E ffects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med., 2008, 358, 2545-2559
4. Currie, C.J.; Poole, C.D.; Gale, E.A. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia, 2009, 52, 1766-1777
5. Johnson, J.A.; Bowker, S.L. Intensive glycaemic control and cancer risk in type 2 diabetes: A meta-analysis of major trials. Diabetologia, 2011, 54, 25-31
6. Nathan, D.M.; Buse, J.B.; Davidson, M.B.; Ferrannini, E.; Holman, R.R.; Sherwin, R.; Zinman, B.; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 2009, 32, 193-203
7. Schernthaner, G.; Barnett, A.H.; Betteridge, D.J.; Carmena, R.; Ceriello, A.; Charbonnel, B.; Hanefeld, M.; Lehmann, R.; Malecki, M.T.; Nesto, R.; Pirags, V.; Scheen, A.; Seufert, J.; Sjohölm, A.; Tsatsoulis, A.; DeFronzo, R. Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis. Diabetologia, 2010, 53, 1258-1269
8. Matteucci, E.; Giampietro, O. Dipeptidyl peptidase-4 (CD26): Knowing the function before inhibiting the enzyme. Curr. Med. Chem., 2009, 16, 2943-2951
9. Mentlein, R.; Gallwitz, B.; Schmidt, W.E. 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 (Pubitemid 23188160)
10. Deacon, C.F.; Hughes, T.E.; Holst, J.J. Dipeptidyl-peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes, 1998, 47, 764-769 (Pubitemid 28201806)
11. Drucker, D.J. Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes. Diabetes Care, 2007, 30, 1335-1343
12. Lambeir, A.-M.; Scharpé, S.; De Meester, I. DPP4 inhibitors for diabetes- What next? Biochem. Pharmacol., 2008, 76, 1637-1643
13. Kim, D.; Wang, L.; Beconi, M.; Eiermann, G.J.; Fisher, M.H.; He, H.; Hickey, G.J.; Kowalchick, J.E.; Leiting, B.; Lyons, K.; Marsilio, F.; McCann, M.E.; Patel, R.A.; Petrov, A.; Scapin, G.; Patel, S.B.; Roy, R.S.; Wu, J.K.; Wyvratt, M.J.; Zhang, B.B.; Zhu, L.; Thornberry, N.A.; Weber, A.E. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3- a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2005, 48, 141-151 (Pubitemid 40105255)
14. Neumiller, J.J.; Wood, L.; Campbell, R.K. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. Pharmacotherapy, 2010, 30, 463-484
15. Brandt, I.; Joossens, J.; Chen, X.; Maes, M.B.; Scharpé, S.; De Meester, I.; Lambeir, A.M. Inhibition of dipeptidyl-peptidase IV catalyzed peptide truncation by Vildagliptin ((2S)-{[(3-hydroxyadamantan-1-yl)amino] acetyl}- pyrrolidine-2-carbonitrile). Biochem. Pharmacol., 2005, 70, 134-143 (Pubitemid 40797877)
16. Fura, A.; Khanna, A.; Vyas, V.; Koplowitz, B.; Chang, S.Y.; Caporuscio, C.; Boulton, D.W.; Christopher, L.J.; Chadwick, K.D.; Hamann, L.G.; Humphreys, W.G.; Kirby, M. Pharmacokinetics of the dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and monkeys and clinical projections. Drug. Metab. Dispos., 2009, 37, 1164-1171
17. Lee, B.; Shi, L.; Kassel, D.B.; Asakawa, T.; Takeuchi, K.; Christopher, R.J. Pharmacokinetic, pharmacodynamic, and efficacy profiles of alogliptin, a novel inhibitor of dipeptidyl peptidase-4, in rats, dogs, and monkeys. Eur. J. Pharmacol., 2008, 589, 306-314
18. Thomas, L.; Eckhardt, M.; Langkopf, E.; Tadayyon, M.; Himmelsbach, F.; Mark. M. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4- methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J. Pharmacol. Exp. Ther., 2008, 325, 175-182 (Pubitemid 351439162)
19. Baetta, R.; Corsini, A. Pharmacology of dipeptidyl peptidase-4 inhibitors: Similarities and differences. Drugs, 2011, 71, 1441-1467
20. Lankas GR, Leiting B, Roy RS, Eiermann GJ, Beconi MG, Biftu T, Chan CC, Edmondson S, Feeney WP, He H, Ippolito DE, Kim D, Lyons KA, Ok HO, Patel RA, Petrov AN, Pryor KA, Qian X, Reigle L, Woods A, Wu JK, Zaller D, Zhang X, Zhu L, Weber AE, Thornberry NA. 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 (Pubitemid 41401097)
21. Wu, J.J.; Tang, H.K.; Yeh, T.K.; Chen, C.M.; Shy, H.S.; Chu, Y.R.; Chien, C.H.; Tsai, T.Y.; Huang, Y.C.; Huang, Y.L.; Huang, C.H.; Tseng, H.Y.; Jiaang, W.T.; Chao, Y.S.; Chen, X. Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor. Biochem. Pharmacol., 2009, 78, 203-210
22. Kirby, M.; Yu, D.M.; O'Connor, S.; Gorrell, M.D. Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition. Clin. Sci., 2009, 118, 31-41
23. Yu, D.M.; Yao, T.W.; Chowdhury, S.; Nadvi, N.A.; Osborne, B.; Church, W.B.; McCaughan, G.W.; Gorrell, M.D. The dipeptidyl peptidase IV family in cancer and cell biology. FEBS. J., 2010, 277, 1126-1144
24. Iwaki-Egawa, S.; Watanabe, Y.; Fujimoto, Y. CD26/dipeptidyl peptidase IV does not work as an adenosine deaminase-binding protein in rat cells. Cell. Immunol., 1997, 178, 180-186 (Pubitemid 27397601)
25. Blech, S.; Ludwig-Schwellinger, E.; Gräfe-Mody, E.U.; Withopf, B.; Wagner, K. The metabolism and disposition of the oral dipeptidyl peptidase- 4 inhibitor, linagliptin, in humans. Drug. Metab. Dispos., 2010, 38, 667-678
26. Seck, T.; Nauck, M.; Sheng, D.; Sunga, S.; Davies, M.J.; Stein, P.P.; Kaufman, K.D.; Amatruda, J.M.; Sitagliptin Study 024 Group. Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: A 2-year study. Int. J. Clin. Pract., 2010, 64, 562-576
27. Barzilai, N.; Guo, H.; Mahoney, E.M.; Caporossi, S.; Golm, G.T.; Langdon, R.B.; Williams-Herman, D.; Kaufman, K.D.; Amatruda, J.M.; Goldstein, B.J.; Steinberg, H. Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: A randomized, double-blind, placebocontrolled trial. Curr. Med. Res. Opin., 2011, 27, 1049-1058
28. Yoon, K.H.; Shockey, G.R.; Teng, R.; Golm, G.T.; Thakkar, P.R.; Meehan, A.G.; Williams-Herman, D.E.; Kaufman, K.D.; Amatruda, J.M.; Steinberg, H. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycemic control and measures of ć-cell function in patients with type 2 diabetes. Int. J. Clin. Pract., 2011, 65, 154-164
29. Hermansen, K.; Kipnes, M.; Luo, E.; Fanurik, D.; Khatami, H.; Stein, P.; Sitagliptin Study 035 Group. Efficacy and safety of the dipeptidyl peptidase- 4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes. Metab., 2007, 9, 733-745 (Pubitemid 47261855)
30. Hollander, P.; Raslova, K.; Skjøth, T.V.; Råstam, J.; Liutkus, J.F. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: The TRANSITION randomized controlled trial. Diabetes Obes. Metab., 2011, 13, 268-275
31. Filozof, C.; Gautier, J.F. A comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with Type 2 diabetes inadequately controlled with metformin alone: A 52-week, randomized study. Diabet. Med., 2010, 27, 318-326
32. Göke, B.; Hershon, K.; Kerr, D.; Calle Pascual, A.; Schweizer, A.; Foley, J.; Shao, Q.; Dejager, S. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naïve patients with type 2 diabetes: C omparison with metformin. Horm. Metab. Res., 2008, 40, 892-895
33. Schweizer, A.; Dejager, S.; Foley, J.E.; Couturier, A.; Ligueros-Saylan, M.; Kothny, W. Assessing the cardio-cerebrovascular safety of vildagliptin: Meta-analysis of adjudicated events from a large Phase III type 2 diabetes population. Diabetes Obes. Metab., 2010, 12, 485-494
34. Waugh, N.; Cummins, E.; Royle, P.; Clar, C.; Marien, M.; Richter, B.; Philip, S. Newer agents for blood glucose control in type 2 diabetes: Systematic review and economic evaluation. Health Technol. Assess., 2010, 14, 1-248
35. Williams-Herman, D.; Engel, S.S.; Round, E.; Johnson, J.; Golm, G.T.; Guo, H.; Musser, B.J.; Davies, M.J.; Kaufman, K.D.; Goldstein, B.J. Safety and tolerability of sitagliptin in clinical studies: A pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr. Disord., 2010, 10, 7
36. Vella, A.; Bock, G.; Giesler, P.D.; Burton, D.B.; Serra, D.B.; Saylan, M.L.; Dunning, B.E.; Foley, J.E.; Rizza, R.A.; Camilleri, M. Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes, 2007, 56, 1475-1480 (Pubitemid 46715627)
37. Hellström, P.M. GLP-1 playing the role of a gut regulatory compound. Acta Physiol., 2011, 201, 151-156
38. Miki, T.; Minami, K.; Shinozaki, H.; Matsumura, K.; Saraya, A.; Ikeda, H.; Yamada, Y.; Holst, J.J.; Seino, S. Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility. Diabetes, 2005, 54, 1056-1063 (Pubitemid 40446319)
39. Holst, J.J. The physiology of glucagon-like peptide 1. Physiol. Rev., 2007, 87, 1409-1439 (Pubitemid 350041474)
40. Paschetta, E.; Hvalryg, M.; Musso G. Glucose-dependent insulinotropic polypeptide: From pathophysiology to therapeutic opportunities in obesityassociated disorders. Obes. Rev., 2011, doi: 10.1111/j.1467- 789X.2011.00897.x
41. Asmar, M. New physiological effects of the incretin hormones GLP-1 and GIP. Dan. Med. Bull., 2011, 58, B4248
42. Yoder, S.M.; Yang, Q.; Kindel, T.L.; Tso, P. Stimulation of incretin secretion by dietary lipid: Is it dose dependent? Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 297, G299-305
43. Rudovich, N.N.; Nikiforova, V.J.; Otto, B.; Pivovarova, O.; Gögebakan, O.; Erban, A.; Möhlig, M.; Weickert, M.O.; Spranger, J.; Tschöp, M.H.; Willmitzer, L.; Nauck, M.A.; Pfeiffer, A.F. Metabolomic linkage unveils functional interaction between Glucose-dependent Insulinotropic Peptide (GIP) and Ghrelin in Humans. Am. J. Physiol. Endocrinol. Metab., 2011, doi: 10.1152/ajpendo.00154
44. Engel, S.S.; Williams-Herman, D.E.; Golm, G.T.; Clay, R.J.; Machotka, S.V.; Kaufman, K.D.; Goldstein, B.J. Sitagliptin: Review of preclinical and clinical data regarding incidence of pancreatitis. Int. J. Clin. Pract., 2010, 64, 984-990
45. Ligueros-Saylan, M.; Foley, J.E.; Schweizer, A.; Couturier, A.; Kothny, W. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials. Diabetes Obes. Metab., 2010, 12, 495-509
46. Elashoff, M.; Matveyenko, A.V.; Gier, B.; Elashoff, R.; Butler, PC. Pancreatitis, pancreatic and thyroid cancer with glucagon like peptide-1- based therapies. Gastroenterology, 2011, 141, 150-156
47. Matveyenko, A.V.; Dry, S.; Cox, H.I.; Moshtaghian, A.; Gurlo, T.; Galasso, R.; Butler, A.E.; Butler, P.C. Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: Interactions with metformin. Diabetes, 2009, 58, 1604-1615
48. Koehler, J.A.; Baggio, L.L.; Lamont, B.J.; Ali, S.; Drucker, D.J. Glucagonlike peptide-1 receptor activation modulates pancreatitis-associated gene expression but does not modify the susceptibility to experimental pancreatitis in mice. Diabetes, 2009, 58, 2148-2161
49. Garg, R.; Chen, W.; Pendergrass, M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: A retrospective observational pharmacy claims analysis. Diabetes Care, 2010, 33, 2349-2354
50. Brown, N.J.; Byiers, S.; Carr, D.; Maldonado, M.; Warner, B.A. Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitorassociated angioedema. Hypertension, 2009, 54, 516-523
51. Gorrell, M.D. Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin. Sci., 2005, 108, 277-292 (Pubitemid 40516992)
52. Forssmann, U.; Stoetzer, C.; Stephan, M.; Kruschinski, C.; Skripuletz, T.; Schade, J.; Schmiedl, A.; Pabst, R.; Wagner, L.; Hoffmann, T.; Kehlen, A.; Escher, S.E.; Forssmann, W.G.; Elsner, J.; von Hörsten, S. Inhibition of CD26/dipeptidyl peptidase IV enhances CCL11/eotaxin-mediated recruitment of eosinophils in vivo. J. Immunol., 2008, 181, 1120-1127
53. Wood, S.H.; Clements, D.N.; Ollier, W.E.; Nuttall, T.; McEwan, N.A.; Carter, S.D. Gene expression in canine atopic dermatitis and correlation with clinical severity scores. J. Dermatol. Sci., 2009, 55, 27-33
54. Christopherson, K. W.; Hangoc, G.; Mantel, C.R.; Broxmeyer, H. E. Modulation of hematopoietic stem cell homing and engraftment by CD26. Science, 2004, 305, 1000-1003 (Pubitemid 39071774)
55. Jost, M.M.; Lamerz, J.; Tammen, H.; Menzel, C.; De Meester, I.; Lambeir, A.M.; Augustyns, K.; Scharpé, S.; Zucht, H.D.; Rose, H.; Jürgens, M.; Schulz-Knappe, P.; Budde, P. In vivo profiling of DPP4 inhibitors reveals alterations in collagen metabolism and accumulation of an amyloid peptide in rat plasma. Biochem. Pharmacol., 2009, 77, 228-237
56. Martinez-Navio, J.M.; Casanova, V.; Pacheco, R.; Naval-Macabuhay, I.; Climent, N.; Garcia, F.; Gatell, J.M.; Mallol, J.; Gallart, T.; Lluis, C.; Franco, R. Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells. J. Leukoc. Biol., 2011, 89, 127-136
57. Ohnuma, K.; Dang, N.H.; Morimoto, C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol., 2008, 29, 295-301
58. Liu, Z.; Christensson, M.; Forslöw, A.; De Meester, I.; Sundqvist, K.G. A CD26-controlled cell surface cascade for regulation of T cell motility and chemokine signals. J. Immunol., 2009, 183, 3616-3624
59. Klemann, C.; Schade, J.; Pabst, R.; Leitner, S.; Stiller, J.; von Hörsten, S.; Stephan, M. CD26/dipeptidyl peptidase 4-deficiency alters thymic emigration patterns and leukcocyte subsets in F344-rats age-dependently. Clin. Exp. Immunol., 2009, 155, 357-365
60. Tian, L.; Gao, J.; Hao, J.; Zhang, Y.; Yi, H.; O'Brien, T.D.; Sorenson, R.; Luo, J.; Guo, Z. Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor. Endocrinology, 2010, 151, 3049-3060
61. Kim, S.J.; Nian, C.; Doudet, D.J.; McIntosh, C.H. Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes, 2009, 58, 641-651
62. Pitocco, D.; Zaccardi, F.; Martini, F.; Scavone, G.; Musella, T.; Caputo, S.; Ghirlanda, G. Severe leucopenia associated with Sitagliptin use. Diabetes Res. Clin. Pract., 2011, 91, e30-22
63. Rosenstock, J.; Sankoh, S.; List, J.F. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes. Metab., 2008, 10, 376-386 (Pubitemid 351524285)
64. Amori, R.E.; Lau, J.; Pittas, A.G. Efficacy and safety of incretin therapy in type 2 diabetes: Systematic review and meta-analysis. JAMA., 2007, 298, 194-206 (Pubitemid 47057766)
65. Richter, B.; Bandeira-Echtler, E.; Bergerhoff, K.; Lerch, C.L. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst. Rev., 2008, CD006739
66. White, P.C.; Chamberlain-Shea, H.; de la Morena, M.T. Sitagliptin treatment of patients with type 2 diabetes does not affect CD4+ T-cell activation. J. Diabetes Complications., 2010, 24, 209-213
67. Wheway, J.; Mackay, C.R.; Newton, R.A.; Sainsbury, A.; Boey, D.; Herzog, H.; Mackay, F. A fundamental bimodal role for neuropeptide Y1 receptor in the immune system. J. Exp. Med., 2005, 202, 1527-1538 (Pubitemid 41746599)
68. Reinhold, D.; Bank, U.; Bühling, F.; Lendeckel, U.; Faust, J.; Neubert, K.; Ansorge, S. Inhibitors of dipeptidyl peptidase IV induce secretion of transforming growth factor-beta 1 in PWM-stimulated PBMC and T cells. Immunology, 1997, 91, 354-360 (Pubitemid 27304270)
69. Steinbrecher, A.; Reinhold, D.; Quigley, L.; Gado, A.; Tresser, N.; Izikson, L.; Born, I.; Faust, J.; Neubert, K.; Martin, R.; Ansorge, S.; Brocke, S. Targeting dipeptidyl peptidase IV (CD26) suppresses autoimmune encephalomyelitis and up-regulates TGF-beta 1 secretion in vivo. J. Immunol., 2001, 166, 2041-2048 (Pubitemid 32114693)
70. Ganea, D.; Gonzalez-Rey, E.; Delgado, M. A novel mechanism for immunosuppression: From neuropeptides to regulatory T cells. J. Neuroimmune Pharmacol., 2006, 1, 400-409 (Pubitemid 44786673)
71. Sauvé, M.; Ban, K.; Momen, M.A.; Zhou, Y.Q.; Henkelman, R.M.; Husain, M.; Drucker, D.J. Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice. Diabetes, 2010, 59, 1063-1073
72. Ogawa, S.; Ishiki, M.; Nako, K.; Okamura, M.; Senda, M.; Mori, T.; Ito, S. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes. Tohoku J. Exp. Med., 2011, 223, 133-135
73. Pacheco, B.P.; Crajoinas, R.O.; Couto, G.K.; Davel, A.P.; Lessa, L.M.; Rossoni, L.V.; Girardi, A.C. Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats. J. Hypertens., 2011, 29, 520-528
74. Tang-Christensen, M.; Vrang, N.; Larsen, P.J. Glucagon-like peptide 1(7-36) amide's central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment. Diabetes., 1998, 47, 530-537 (Pubitemid 28160441)
75. Hattori, S. Sitagliptin reduces albuminuria in patients with type 2 diabetes. Endocr. J., 2011, 58, 69-73
76. Marney, A.; Kunchakarra, S.; Byrne, L.; Brown, N.J. Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensinconverting enzyme inhibition in humans. Hypertension., 2010, 56, 728-733
77. Matheeussen, V.; Baerts, L.; De Meyer, G.; De Keulenaer, G.; Van der Veken, P.; Augustyns, K.; Dubois, V.; Scharpé, S.; De Meester, I. Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries. Biol. Chem., 2011, 392, 189-198
78. Takasawa, W.; Ohnuma, K.; Hatano, R.; Endo, Y.; Dang, N.H.; Morimoto, C. Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines. Biochem. Biophys. Res. Commun., 2010, 401, 7-12
79. Fadini, G.P.; Boscaro, E.; Albiero, M.; Menegazzo, L.; Frison, V.; de Kreutzenberg, S.; Agostini, C.; Tiengo, A.; Avogaro, A. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: Possible role of stromal-derived factor- 1alpha. Diabetes Care., 2010, 33, 1607-1609
80. Cordero, O.J.; Salgado, F.J.; Nogueira, M. On the origin of serum CD26 and its altered concentration in cancer patients. Cancer Immunol. Immunother., 2009, 58, 1723-1747
81. Songok, E.M.; Osero, B.; McKinnon, L.; Rono, M.K.; Apidi, W.; Matey, E.J.; Meyers, A.F.; Luo, M.; Kimani, J.; Wachihi, C.; Ball, B.T.; Plummer, F.A.; Mpoke, S. CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected female sex workers. Virol. J., 2010, 7, 343
82. Casrouge, A.; Decalf, J.; Ahloulay, M.; Lababidi, C.; Mansour, H.; Vallet- Pichard, A.; Mallet, V.; Mottez, E.; Mapes, J.; Fontanet, A.; Pol, S.; Albert, M.L. Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV. J. Clin. Invest., 2011, 121, 308-317
83. Fletcher, M.A.; Zeng, X.R.; Maher, K.; Levis, S.; Hurwitz, B.; Antoni, M.; Broderick, G.; Klimas, N.G. Biomarkers in chronic fatigue syndrome: E valuation of natural killer cell function and dipeptidyl peptidase IV/CD26. PLoS One, 2010, 5, e10817
84. Qin, X.; Shen, H.; Liu, M.; Yang, Q.; Zheng, S.; Sabo, M.; D'Alessio, D.A.; Tso, P. GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 288, G943-949 (Pubitemid 40563135)
85. Ebert, R.; Nauck, M.; Creutzfeldt, W. Effect of exogenous or endogenous gastric inhibitory polypeptide (GIP) on plasma triglyceride responses in rats. Horm. Metab. Res., 1991, 23, 517-521
86. Matikainen, N.; Mänttäri, S.; Schweizer, A.; Ulvestad, A.; Mills, D.; Dunning, B.E.; Foley, J.E.; Taskinen, M.R. Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes. Diabetologia, 2006, 49, 2049-2057 (Pubitemid 44168471)
87. Sato, Y.; Koshioka, S.; Kirino, Y.; Kamimoto, T.; Kawazoe, K.; Abe, S.; Minakuchi, K.; Nakahori, Y. Role of dipeptidyl peptidase IV (DPP4) in the development of dyslipidemia: DPP4 contributes to the steroid metabolism pathway. Life Sci., 2011, 88, 43-49
88. Kuo, L.E.; Kitlinska, J.B.; Tilan, J.U.; Li, L.; Baker, S.B.; Johnson, M.D.; Lee, E.W.; Burnett, M.S.; Fricke, S.T.; Kvetnansky, R.; Herzog, H.; Zukowska, Z. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat. Med., 2007, 13, 803-811 (Pubitemid 47038195)
89. Kos, K.; Baker, A.R.; Jernas, M.; Harte, A.L.; Clapham, J.C.; O'Hare, J.P.; Carlsson, L.; Kumar, S.; McTernan, P.G. DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue. Diabetes Obes. Metab., 2009, 11, 285-292
90. Conarello, S.L.; Li, Z.; Ronan, J.; Roy, R.S.; Zhu, L.; Jiang, G.; Liu, F.; Woods, J.; Zycband, E.; Moller, D.E.; Thornberry, N.A.; Zhang, B.B. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc. Natl. Acad. Sci. U S A., 2003, 100, 6825-6830 (Pubitemid 36666664)
91. 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