N-terminal acetylation protects glucagon-like peptide GLP-1-(7-34)-amide from DPP-IV-mediated degradation retaining cAMP- and insulin-releasing capacity

European Journal of Medical Research

Volumn 13, Issue 2, 2008, Pages 73-78

  John, Harald ^a,d   Maronde, Erik ^b   Forssmann, Wolf Georg ^a,c   Meyer, Markus ^a   Adermann, Knut ^a  

^a IPF PHARMACEUTICALS GMBH   (Germany)

^b GOETHE UNIVERSITY   (Germany)

^c HANNOVER MEDICAL SCHOOL   (Germany)

^d BUNDESWEHR INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY   (Germany)

Author keywords

Acetylation; Dipeptidyl peptidase IV; GLP 1; Glucagon like peptide 1; MALDI TOF MS; Stability

Indexed keywords

ACETYL GLUCAGON LIKE PEPTIDE 1 [7-34] AMIDE; CYCLIC AMP; DIPEPTIDYL PEPTIDASE IV; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 [7-34] AMIDE; GLUCAGON LIKE PEPTIDE 1 [7-36] AMIDE; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; INSULIN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CATALYSIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACETYLATION; DRUG FORMULATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG STABILITY; ENZYME ACTIVITY; INSULIN RELEASE; INSULINOMA; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; NONHUMAN; NUCLEIC ACID SYNTHESIS; RAT;

ACETYLATION; AMIDES; ANIMALS; ANTIGENS, CD26; CELLS, CULTURED; CYCLIC AMP; GLUCAGON-LIKE PEPTIDE 1; INSULIN; INSULINOMA; RATS; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION;

EID: 40749110680     PISSN: 09492321     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (43)

1. Morgan L, Elliott R, Tredger J, Nightingale J, Marks V. GLP-1 secretion in response to nutrients in man. Digestion. 1993; 54: 374-76.
2. Göke R, Richter G, Kolligs F, Fehmann HC, Arnold R, Göke B. How do individual meal constituents influence the release of GLP-1 in humans? Digestion. 1993; 54: 380.
3. Herrmann C, Göke R, Richter G, Fehmann HC, Arnold R, Göke B. Glucagon-like peptide-1 and glucose-dependent insulinreleasing polypeptide plasma levels in response to nutrients. Digestion. 1995; 56: 117-26.
4. Mojsov S. Structural requirements for biological activity of glucagon-like peptide-1. Int J Pept Protein Res. 1992; 40: 333-43.
5. Thorens B. Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci USA. 1992; 89: 8641-45.
6. Dillon JS, Tanizawa Y, Wheeler MB, Leng X-H, Ligon BB, Rabin DU, Yoo-Warren H, Permutt MA, Boyd AE. Cloning and functional expression of the human glucagon-like peptide-1. Endocrinology. 1993; 133: 1907-10.
7. Lu M, Wheeler MB, Leng XH, Boyd AE. The roles of cAMP levels and free cytosolic calcium concentrations in the insulin secretion and insulin gene expression stimulated by glucagon-like peptide 1. Digestion. 1993; 54: 349-51.
8. Wheeler MB, Lu M, Dillon JS, Leng XH, Chen C, Boyd AE. Functional expression of the rat glucagon-like peptide-1 receptor, evidence for coupling to both adenyl cyclase and phospholipase-C. Endocrinology. 1993; 133: 57-62.
9. Wheeler MB, Lu M, Dillon JS, Leng XH, Boyd JS. The rat glucagon-like peptide-1 receptor can couple to adenyl cyclase, phospholipase C and the free cytosolic calcium level. Digestion. 1993; 54: 348-49.
10. Mojsov S, Weir GC, Habener JF. Insulinotropin: glucagon-like peptide-1 (7-37), coencoded in the glucagon gene is a potent stimulator of insulin release in the perfused pancreas. J Clin Invest. 1987; 79: 616-19.
11. Orskov C. Glucagon-like peptide-1, a new hormone of the enteroinsular axis. Diabetologia. 1992; 35: 701-11.
12. Orskov C, Holst JJ, Nielsen OV. Effect of truncated glucagon-like peptide-1 (proglucagon 78-107) on endocrine secretion from pig pancreas, antrum and stomach. Endocrinology. 1988; 123: 2009-13.
13. D'Alessio, DA, Fujimoto WT, Ensinck JW. Effects of glucagons like peptide-1 (7-36) on release of insulin, glucagon, and somatostatin by rat pancreas islet cell monolayer cultures. Diabetes. 1989; 38: 1534-38.
14. Matsumura T, Itoh H, Watanabe N, Oda Y, Tanaka M, Namba M, Kono N, Matsuyama T, Komatsu R, Matsuzawa Y. Glucagon-like peptide-1 (7-36) amide suppresses glucagon secretion and decreases cyclic AMP concentration in cultured In-R1-G9 cells. Biochem Biophys Res Commun. 1992; 186: 503-8.
15. Gutniak M, Orskov C, Holst JJ, Ahren B, Effendic S. Antidiabetogenic effect of glucagon-like peptide-1 (7-36) amide in normal subjects and patients with diabetes mellitus. N Engl J Med. 1992; 326: 1316-22.
16. Thorens B, Waeber G. Glucagon-like peptide-1 and the control of insulin secretion in the normal state and in NIDDM. Diabetes. 1993; 42:1219-25.
17. Gutniak MK, Linde B, Efendic S. Subcutaneous injection of glucagon-like insulinotropic peptide reduces postprandial glycaemia in non-insulin-dependent diabetes. Digestion. 1993; 54: 389-90.
18. Hendrick GK, Gjinovici A, Baxter LA, Mojsov S, Wollheim CB, Habener JF, Weir GC. Glucagon-like peptide-1 (7-36) suppresses hyperglycemia in rats. Metabolism. 1993;42:1-6.
19. Nauk MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 (7-36) amide but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993; 91: 301-7.
20. Nauk MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36) amide in type 2 (non-insulin-dependent) diabetic patients. Digestion. 1993; 54: 389.
21. Qualmann C, Nauck MA, Holst JJ, Orskov C, Creutzfeldt W. Insulinotropic actions of intravenous glucagon-like peptide 1 (GLP-1) 7-36 amide.in the fasting state in healthy subjects. Acta Diabetologica. 1995; 32: 13-6.
22. 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: 952-7.
23. Kieffer TJ, McIntosh HS, 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: 3585-96.
24. Xiao Q, Giguere J, Parisien M, Jeng W, St-Pierre SA, Brubaker PL, Wheeler MB. Biological activities of glucagon-like peptide-1 analogies in vitro and in vivo. Biochemistry. 2001; 40: 2860-69.
25. Siegel EG, Gallwitz B, Scharf G, Mentlein R, Morys-Wortmann C, Fösch UR, Schrezenmeir J, Drescher K, Schmidt WE. Biological activity of GLP-1 analogues with N-terminal modifications. Regul Pept. 1999; 79: 93-102.
26. De Menthière CS, Chavanieu A, Grassy G, Dalle S, Salazar G, Kervran A, Pfeiffer B, Renard P, Delagrange P, Manechez D, Bakes D, Ktorza A, Calas B. Structural requirements of the N-terminal region of GLP-1-7-37]-NH2 for receptor interaction and cAMP production. Eur J Med Chem. 2004; 39: 473-80.
27. Adelhorst K, Hedegaard BB, Knudsen LB, Kirk O. Structure-activity studies of glucagon-like peptide-1. J Biol Chem. 1994; 269: 6275-8.
28. Youn YS, Chae SY, Lee S, Jeon JE, Shin HG, Lee KC. Evaluation of therapeutic potentials of site-specific PEGylated glucagon-like peptide-1 isomers as a type 2 antidiabetic treatment: Insulinotropic activity, glucose-stabilizing capability, and proteolytic stability. Biochem Pharmacol. 2006; 73: 84-93.
29. Lee SH, Lee S, Youn YS, Na DH, Chae SY, Byun Y, Lee KC. Synthesis, characterization, and pharmacokinetic studies of PEGylated glucagon-like peptide-1. Bioconjug Chem. 2005; 16: 377-82.
30. Léger R, Thibaudeau K, Robitaille M, Quraishi O, van Wyk P, Bousquet-Gagnon N, Carette J, Castaigne JP, Bridon DP. Identification of CJC-1131 -albumin bioconjugate as a stable and bioactive GLP-1(7-36) analogue. Bioorg Med Chem Lett. 2004; 14: 4395-8.
31. Knudsen LB, Nielsen PF, Huusfeldt PO, Johansen NL, Madsen K, Pedersen FZ, Thøgersen H, Wilken M, Agersø H. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem. 2000; 43: 1664-9.
32. Larsen PJ, Fledelius C, Knudsen LB, Tang-Christensen M. Systemic administration of the long-acting GLP-1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes. 2001; 50: 2530-9.
33. Burcelin R, Dolci W, Thorens B. Long-lasting antidiabetic effect of a dipeptidyl peptidase IV-resistant analogue of glucagon-like peptide-1. Metabolism. 1999; 48: 252-8.
34. Ritzel U, Leonhardt U, Ottleben M, Rühmann A, Eckart K, Spiess J, Ramadori G. A synthetic glucagon-like peptide-1 analogue with improved plasma stability. J Endocrinol. 1998; 159: 93-102.
35. Green BD, Lavery KS, Irwin N, O'harte FP, Harriott P, Greer B, Bailey CJ, Flatt PR. Novel glucagon-like peptide-1 (GLP-1) analogue (Val8)GLP-1 results in significant improvements of glucose tolerance and pancreatic beta-cell function after 3-week daily administration in obese diabetic (ob/ob) mice. J Pharmacol Exp Ther. 2006; 318: 914-21.
36. Doyle ME, Greig NH, Holloway HW, Berkey JA, Bernier M, Egan JM. Insertion of an N-terminal 6-aminohexanoic acid after the 7 amino acid position of glucagon-like peptide-1 produces a long-acting hypoglycemic agent. Endocrinology. 2001; 142: 4462-68.
37. John H, Schulz S, Forssmann WG. Comparative in vitro degradation of the human hemorphin LVV-H7 in mammalian plasma analyzed by capillary zone electrophoresis and mass spectrometry. Biopharm Drug Dispos. 2007; 28: 73-85.
38. Fricke K, Schulz A, John H, Forssmann WG, Maronde E. Isolation and characterization of a novel proopiomelanocortin-derived peptide from hemofiltrate of chronic renal failure patients. Endocrinology. 2005; 146: 2060-68.
39. Stephan S, van de Flierdt J, Loumi S, Bonaterra G, Kramer FJ, Fehr M, Tillmann HC, Forssmann WG, Maronde E. Intermittent administration of the circulating form of human parathyroid hormone (hPTH-1-37) prevents bone loss in ovariectomized rats. Eur J Med Res. 2007; 12(1):13-20.
40. Pauly RP, Rosche F, Wermann M, McIntosh CHS, 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. J Biol Chem. 1996; 271: 23222-29.
41. Zhu L, Tamvakopoulos C, Xie D, Dragovic J, Shen X, Fenyk-Melody JE, Schmidt K, Bagchi A, Griffin PR, Thornberry NA, Sinha Roy, R. 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: 22418-23.
42. Suzuki S, Kawai K, Ohashi S, Mukai H, Yamashita K. Comparison of the effects of various C-terminal and N-terminal fragment peptides of glucagon-like peptide-1 on insulin and glucazon release from the isolated perfused rat pancreas. Endocrinology. 1989; 125: 3109-14.
43. Gefel D, Hendrick GK, Mojsov S, Habener J, Weir GC. Glucagon-like peptide-I analogs: effects on insulin secretion and adenosine 3′,5′-monophosphate formation. Endocrinology. 1990; 126: 2164-8.