Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement

Current Opinion in Investigational Drugs

Volumn 7, Issue 4, 2006, Pages 338-343

  Mest, Hans Juergen ^a  

^a LILLY DEUTSCHLAND GMBH   (Germany)

Author keywords

DPP IV inhibitors; GIP; GLP 1; Glucose homeostasis; Incretins; Type 2 diabetes

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; 3 AMINO 1 [5,6,7,8 TETRAHYDRO 3 (TRIFLUOROMETHYL) 1,2,4 TRIAZOLO[4,3 A]PYRAZIN 7 YL] 4 (2,4,5 TRIFLUOROPHENYL) 1 BUTANONE; ANTIDIABETIC AGENT; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCOSE; INCRETIN; INSULIN SENSITIZING AGENT; METFORMIN; SAXAGLIPTIN; SULFONYLUREA; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ALOPECIA; ANEMIA; BODY WEIGHT DISORDER; CLINICAL TRIAL; DISEASE MODEL; DOSE RESPONSE; DRUG ACTIVITY; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME ACTIVITY; GLUCOSE HOMEOSTASIS; HUMAN; IN VIVO STUDY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; REVIEW; RISK FACTOR; SPLENOMEGALY; THROMBOCYTOPENIA; VOMITING; WEIGHT GAIN; WEIGHT REDUCTION;

ANIMALS; ANTIGENS, CD26; BLOOD GLUCOSE; BODY WEIGHT; CLINICAL TRIALS; DIABETES MELLITUS, TYPE 2; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE 1; HOMEOSTASIS; HUMANS; INSULIN-SECRETING CELLS; PROTEASE INHIBITORS;

EID: 33645780417     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (77)

1. Mannucci E, Pala L, Ciani S, Bardiri G, Pazzatini A, Sposato I, Cremasco F, Ognibene A, Rotella CM: Hyperglycaemia Increases dipeptidyl peptidase IV activity In diabetes mellitus. Diabetologia (2005) 48(6):1168-1172.
2. Holst JJ, Deacon CF: Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia (2005) 48(4):612-615.
3. Mest H-J, Mentlein R: Dipeptidyl peptidase inhibitors as new drugs for the treatment of type 2 diabetes. Diabetologia (2005) 48(4):816-620.
4. Dunning BE, Foley JE, Ahren B: α Cell function in health and disease: Influence of glucagon-like peptide-1. Diabetologia (2005) 48(9):1700-1713.
5. 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(3):829-835.
6. Holst JJ: Glucagon-like peptide-1, a gastrointestinal hormone with a pharmaceutical potential. Curr Med Chem (1999) 6(11):1005-1017.
7. Drucker DJ: Minireview: The glucagon-like peptides. Endocrinology (2001) 142(2):521-527.
8. Drucker DJ: Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology (2002) 122(2):531-544.
9. Sinclair EM, Drucker DJ: Glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase IV inhibitors: New therapeutic agents for the treatment of type 2 diabetes. Curr Opin Endocrinol Diabetes (2005) 12(2):146-151.
10. Nauck MA, El-Ouaghlidi A: The therapeutic actions of DPP-IV inhibition are not mediated by glucagon-like peptide-1. Diabetologia (2005) 48(4):608-611.
11. Ahren 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(4):2055-2059.
12. Hansotia T, Baggio LL, Delmeire D, Hinke SA, Yamada Y, Tsukiyama K, Seino Y, Holst JJ, Schuit F, Drucker DJ: 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(5):1326-1335.
13. Hansotia T, Drucker DJ: GIP and GLP-1 as incretin hormones: Lessons from single and double incretin receptor knockout mice. Regul Pept (2005) 128(2):125-134.
14. Mentlien R: Dipeptidyl-peptidase IV (CD26) - role in the inactivation of regulatory peptides. Regul Pept (1999) 86(1):9-24.
15. Kieffer TJ: GIP or not GIP? That is the question. Trends Pharmacol Sci (2003) 24(3):110-112.
16. Deacon CF, Danielsen P, Klarskov L, Olesen M, Holst JJ: Dipeptidyl peptidase IV inhibition reduces the degradation and clearance of GIP and potentiates its insulinotropic and antihyperglycemic effects in anesthetized pigs. Diabetes (2001) 50(7):1588-1597.
17. Vilsboll T, Krarup T, Madsbad S, Holst JJ: Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept (2003) 114(2-3):115-121.
18. Vilsboll T: On the role of the incretin hormones GIP and GLP-1 in the pathogenesis of type 2 diabetes mellitus. Dan Med Bull (2004) 51(4):384-370.
19. Delmeire D, Flamez D, Moens K, Hinke SA, Van Schravendijk C, Pipeleers D, Schuit F: Prior in vitro exposure to GLP-1 with or without GIP can influence the subsequent β cell responsiveness. Biochem Pharmacol (2004) 68(1):33-39.
20. Hui H, Farilla L, Merkel P, Perfetti R: The short half-life of glucagon-like peptide-1 in plasma does not reflect its long-lasting beneficial effects. Eur J Endocrinol (2002) 146(6):883-869.
21. Yada T, Sakurada M, Ihida K, Nakata M, Murata F, Arimura A, Kikuchi M: Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet β-cells. J Biol Chem (1994) 269(2):1290-1293.
22. Yada T, Sakurada M, Filipsson K, Kikuchi M, Ahren B: Intraperitoneal PACAP administration decreases blood glucose in GK rats, and in normal and high fat diet mice. Ann NY Acad Sci (2000) 921:259-263.
23. Yamamoto K, Hashimoto H, Tomimoto S, Shintani N, Miyazaki J-I, Tashiro F, Aihara H, Nammo T, Li M, Yamagata K, Miyagawa J-I et al: Overexpression of PACAP in transgenic mouse pancreatic β-cells enhances insulin secretion and ameliorates streptozotocin-induced diabetes. Diabetes (2003) 52(5):1155-1162.
24. Lugari P, Dei Cas A, Ugolotti D, Finardi L, Barilli AL, Ognibene C, Luciani A, Zandomeneghi R, Gnudi A: Evidence for early impairment of glucagon-like peptide 1-induced insulin secretion in human type 2 (non insulin-dependent) diabetes. Horm Metab Res (2002) 134(3):150-154.
25. Lugari R, Dei Cas A, Ungolotti D, Barilli AL, Camellini C, Ganzerla GC, Luciani A, Salemi B, Mittenperger F, Nordari S, Gnudi A, Zandomeneghi R: Glucagon-like peptide 1 (GLP-1) secretion and plasma dipeptidyl peptidase IV (DPP-IV) activity in morbidity obese patients undergoing biliopancreatic diversion. Horm Metab Res (2004) 38(2):111-115.
26. Frezza EE: Are we closer to finding the treatment tor type 2 diabetes mellitus in morbid obesity? Are the incretins the key to success? Obes Surg (2004) 14(7):999-1005.
27. Gault VA, Flatt PR, O'Harte FPM: Glucose-dependent insulinotropic polypeptide analogues and their therapeutic potential for the treatment of obesity-diabetes. Biochem Biophys Res Commun (2003) 308(2):207-213.
28. Gutzwiller JP, Drewe J, Goke B, Schmidt H, Rohrer B, Lareida J, Beglinger C: Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol (1999) 276(5 Pt 2):R1541-R1544.
29. Meier JJ, Gallwitz B, Schmidt WE, Nauck MA: Glucagon-like peptide 1 as a regulator of food intake and body weight: Therapeutic perspectives. Eur J Pharmacol (2002) 440(2-3):269-279.
30. Morley JE: An approach to the development of drugs for appetite disorders. Neuropsychobiology (1989) 21(1):22-30.
31. Chamorro S, Della-Zuana O, Fauchere J-L, Feletou M, Galizzi J-P, Levens N: Appetite suppression based on selective inhibition of NPY receptors. Int J Obes Relat Metab Disord (2002) 26(3):281-298.
32. Renshaw D, Batterham RL: Peptide YY: A potential therapy for obesity. Curr Drug Targets (2005) 6(2):171-179.
33. 3-36 synergistically reduce food intake through different mechanisms in mice. Endocrinology (2005) 146(9):3748-3756.
34. Stock S, Leichner P, Wong ACK, Ghatei MA, Kieffer TJ, Bloom SR, Chanoine J-P: Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents. J Clin Endocrinol Metab (2005) 90(4):2161-2168.
35. Small CJ, Parkinson JR, Bloom SR: Novel therapeutic targets for appetite regulation. Curr Opin Investig Drugs (2005) 6(4):369-372.
36. Hildebrandt M, Rose M, Mönnikes H, Reutter W, Keller W, Klapp BF: Eating disorders: A role for dipeptidyl peptidase IV in nutritional control. Nutrition (2001) 17(8):451-454.
37. Marguet D, Baggio L, Kobayashi T, Bernard A-M, Pierres M, Nielsen PF, Ribel U, Watanabe T, Drucker DJ, Wagtmann N: Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA (2000) 97(12):6874-6879.
38. Nagakura T, Yasuda N, Yamazaki K, Ikuta H, Yoshikawa S, Asano O, Tanaka I: Improved glucose tolerance via enhanced glucose-dependent insulin secretion on dipeptidyl peptidase IV-deficient Fischer rats. Biochem Biophys Res Commun (2001) 284(2):501-506.
39. Conarello SL, Li Z, Ronan J, Roy RS, Zhu L, Jiang G, Liu F, Woods J, Zycband E, Moller DE, Thomberry NA, Zhang BB: Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci USA (2003) 100(11):6825-6830.
40. Yasuda N, Nagakura TN, 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(2):227-238.
41. Meier JJ, Nauck MA: GIP as a potential therapeutic agent? Horm Metab Res (2004) 36(11-12):859-866.
42. Yasuda N, Inoue T, Nagakura T, Yamazaki K, Kira K, Saeki T, Tanaka I: Metformin causes reduction of food intake and body weight gain and improvement of glucose intolerance in combination with dipeptidyl peptidase IV inhibitor in Zucker fa/fa rats. J Pharmacol Exp Ther (2004) 310(2):614-619.
43. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CMB, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP et al: A role for glucagon-like peptide-1 in the central regulation of feeding. Nature (1996) 379(6560):69-72.
44. King PJ: The hypothalamus and obesity. Curr Drug Targets (2005) 6(2):225-240.
45. Gotoh K, Fukagawa K, Fukagawa T, Noguchi H, Kakuma T, Sakata T, Yoshimatsu H: Glucagon-like peptide-1, corticotropin-releasing hormone, and hypothalamic neuronal histamine interact in the leptin-signaling pathway to regulate feeding behavior. FASEB J (2005) 19(9):1131-1133.
46. Adam TCM, Jocken J, Westerterp-Plantenga MS: Decreased glucagon-like peptide 1 release after weight loss in overweight/obese subjects. Obes Res (2005) 13(4):710-716.
47. Mari A, Sallas WM, He YL, Watson C, Ligueros-Saylan M, Dunning BE, Deacon CF, Holst JJ, Foley JE: Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed β-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab (2005) 90(8):4888-4894.
48. Ahren B, Pacini G, Foley JE, Schweizer A: Improved meal-related β-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care (2005) 28(8):1936-1940.
49. Brubaker PL, Drucker DJ: Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology (2004) 145(6):2653-2659.
50. Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ: Glucagon-like peptide-1 receptor signaling modulates β cell apoptosis. J Biol Chem (2003) 278(1):471-478.
51. Li Y, Cao X, Li L-X, Brubaker PL, Edlund H, Drucker DJ: β-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Diabetes (2005) 54(2):482-491.
52. Reimer MK, Holst JJ, Ahren B: Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice. Eur J Endocrinol (2002) 146(5):717-727.
53. Pospisilik JA, Martin J, Doty T, Ehses JA, Pamir N, Lynn FC, Piteau S, Demuth H-U, McIntosh CH, Pederson RA: Dipeptidyl peptidase IV inhibitor treatment stimulates β-cell survival and islet neogenesis in streptozotocin-induced diabetic rats. Diabetes (2003) 52(3):741-750.
54. Stoffers DA, Kieffer TJ, Hussain MA, Drucker DJ, Bonner-Weir S, Habener F, Egan JM: Insulinotropic glucagon-like peptide-1 agonists stimulate expression of homeodomain protein IDX-1 and increase β-cell mass in mouse pancreas. Diabetes (2000) 48(5):741-748.
55. Sato K, Aytac U, Yamochi T, Yamochi T, Ohnuma K, McKee KS, Morimoto C, Dang NH: CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II α and sensitivity to apoptosis induced by topoisomerase II inhibitors. Br J Cancer (2003) 89(7):1366-1374.
56. Baggio LL, Drucker D: Therapeutic approaches to preserve islet mass in type 2 diabetes. Annu Rev Med (2006) 57:265-281.
57. Lankas GR, Leiting B, Roy RS, Eiermann GJ, Beconi MG, Biftu T, Chan CC, Edmondson S, Feeney WP, He H, Ippolito DE 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(10):2988-2994.
58. Ahren B, Simonsson E, Larsson H, Landin-Olsson M, Torgeirsson H, Jansson P-A, Sandqvist M, Bavenholm P, Efendic S, Eriksson JW, Dickinson S, Holmes D: Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care (2002) 25(5):889-875.
59. Ahren B, Gomis R, Standl E, Mills D, Schweizer A: Twelve-and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care (2004) 27(12):2874-2880.
60. Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, Wang A, Simpkins LM, Taunk P, Huang Q, Han SP et al: Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem (2005) 48(15):5025-5037.
61. Bergmann A, Krishna R, Mistry G, Luo W, Liu Q, Stone J, Wang A, Zeng W, Chen L, Dilzer S, Laseter K et al: Dose-proportionality of sitaglipin (MK-0431), an oral dipeptidyl peptidase-IV inhibitor, in healthy volunteers. J Clin Pharmacol (2005) 45:1090.
62. McIntyre JA, Castaner J: Vildagliptin. Drugs Future (2004) 29(9):887-891.
63. Sorbera LA, Castaner J: MK-0431. Agent for type 2 diabetes, dipeptidyl-peptidase IV (CD26) inhibitor. Drugs Future (2005) 30(4):337-343.
64. Ristic S, Byiers S, Foley J, Holmes D: Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: Vildagliptin (LAF237) dose response. Diabetes Obesity Metab (2005) 7(6):692-698.
65. Hinke SA, Kühn-Wache K, Hoffmann T, Pederson RA, McIntosh CHS, Demuth H-U: Metformin effecte on dipeptidylpeptidase IV degradation of glucagon-like peptide-1. Biochem Biophys Res Commun (2002) 291(5):1302-1306.
66. Lindsay JR, Duffy NA, McKillop AM, Ardill J, O'Harte FPM, Flatt PR, Bell PM: Inhibition of dipeptidyl peptidase IV activity by oral metformin in type 2 diabetes. Diabetic Med (2005) 22(5):654-657.
67. Hinke SA, McIntosh CH, Hoffmann T, Kuhn-Wache K, Wagner L, Bär J, Manhart S, Wermann M, Pederson RA, Demuth HU: On combination therapy of diabetes with metformin and dipeptidyl-peptidase IV inhibitors. Diabetes Care (2002) 25(8):1490-1491.
68. Wargent E, Stocker C, Augstein P, Heinke P, Meyer A, Hoffmann T, Subramanian A, Sennitt MV, Demuth H-U, Arch JRS, Cawthorne MA: Improvement of glucose tolerance in Zucker diabetic fatty rats by long-term treatment with the dipeptidyl peptidase inhibitor P32/98: Comparison with and combination with rosiglitazone. Diabetes Obesity Metabol (2005) 7(2):170-181.
69. Karl T, Hoffmann T, Pabst R, won Hösten S: Behavioral effects of neuropeptide Y in F344 rat substrains with a raduced dipeptidyl-peptidase IV activity. Pharmacol Biochem Behav (2003) 75(4):869-879.
70. 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(1):123-134.
71. Lautar SL, Rojas C, Slusher BS, Wozniak KM, Wu Y, Thomas AG, Waldon D, Li W, Ferraris D, Belyalov S: DPPIV Inhibitor blocks mescaline-induced scratching and amphetamine-induced hyperactivity in mice. Brain Res (2005) 1048(1-2):177-184.
72. Perry T, Greig NH: Enhancing central nervous system endogenous GLP-1 receptor pathways tor intervention in Alzheimer's disease. Curr Alzheimer Res (2005) 2(3):377-385.
73. Jun-Ichiro O, Takashi I: A role for glucagon-like peptide-1 in neurons and glias: The perspective as an useful tool in Alzheimer's disease studies. J Pharmacol Sci (2005) 87(Suppl 1):30P.
74. Larsen PJ, Holst JJ: Glucagon-related peptide 1 (GLP-1): Hormone and neurotransmitter. Ragul Pept (2005) 128(2):97-107.
75. Tarrago T, Sabido E, Kogan MJ, de Oliveira E, Giralt E: Primary structure, recombinant expression and homology modeling of human brain prolyl oligopeptidase, an important therapeutic target in the treatment of neuropsychiatric diseases. J Peptide Sci (2005) 11(5):283-287.
76. Maes M, De Meester I, Verkerk R, De Medts P, Wauters A, Vanhoof G, Vandoolaeghe E, Neels H, Scharpe S: Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: Relationships with immune-inflammatory markers. Psychoneuroendocrinology (1997) 22(2):65-78.
77. Guieu R, Fenouillet E, Devaux C, Fajloun Z, Carrega L, Sabatier JM, Sauze N, Marguet D: CD26 modulates noiception in mice via its dipeptidyl-peptidase IV activity. Behav Brain Res (2006) 166(2):230-235.