Comparison of stability, cellular, glucose-lowering and appetite supressing effects of oxyntomodulin analogues modified at the N-terminus

European Journal of Pharmacology

Volumn 743, Issue , 2014, Pages 69-78

  Lynch, Aisling M ^a   Pathak, Nupur ^a   Flatt, Yasmin E ^a   Gault, Victor A ^a   O'Harte, Finbarr P M ^a   Irwin, Nigel ^a   Flatt, Peter R ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

Author keywords

Analogue; Food intake; Glucose homoeostasis; Insulin secretion; Oxyntomodulin

Indexed keywords

CYCLIC AMP; DIPEPTIDYL PEPTIDASE IV; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCAGON RECEPTOR; GLUCOSE; OXYNTOMODULIN; OXYNTOMODULIN DERIVATIVE; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; GLUCOSE BLOOD LEVEL; INSULIN; PEPTIDE;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANIMAL EXPERIMENT; APPETITE; ARTICLE; BIOLOGICAL ACTIVITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG STABILITY; DRUG SYNTHESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCEMIC CONTROL; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INSULIN LIKE ACTIVITY; INSULIN RELEASE; MALE; MOUSE; NONHUMAN; PROTEIN DEGRADATION; PROTEIN MODIFICATION; PROTEIN STABILITY; PROTEIN SYNTHESIS; ANIMAL; C57BL MOUSE; DRUG EFFECTS; HALF LIFE TIME; METABOLISM;

ANIMALS; APPETITE; BLOOD GLUCOSE; CYCLIC AMP; DIPEPTIDYL PEPTIDASE 4; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE; HALF-LIFE; HYPOGLYCEMIC AGENTS; INSULIN; MALE; MICE; MICE, INBRED C57BL; OXYNTOMODULIN; PEPTIDES; RECEPTORS, GLUCAGON;

EID: 84919363202     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2014.09.018     Document Type: Article

References (22)

1. L. Baggio, Q. Huang, T.J. Brown, and D.J. Drucker Oxyntomodulin and glucagon-like peptide differentially regulate murine food intake and energy expenditure Gastroenterology 127 2004 546 558
2. V.K. Bhat, B.D. Kerr, P.R. Flatt, and V.A. Gault A novel GIP-oxynotmodulin hybrid peptide acting through GIP, glucagon and GLP-1 receptors exhibits weight-reducing and anti-diabetic properties Biochem. Pharmacol. 85 2013 1655 1662
3. E. Bianchi, P.E. Carrington, P. Ingallinella, M. Finotto, A. Santoprete, A. Petrov, G. Eiermann, J. Kosinski, D.J. Marsh, A. Pocai, R. SinhaRoy, and A. Pessi A PEGylated analog of the gut hormone oxyntomodulin with long-lasting antihyperglycemic, insulinotropic and anorexigenic activity Bioorg. Med. Chem. 21 2013 7064 7073
4. C.L. Dakin, C.J. Small, R.L. Batterham, N.M. Neary, M.A. Cohen, M. Patterson, M.A. Ghatei, and S.R. Bloom Peripheral oxyntomodulin reduces food intake and body weight gain in rats Endocrinology 145 2004 2687 2695
5. M.R. Druce, J.S. Minnion, B.C. Field, S.R. Patel, J.C. Shillito, M. Tilby, K.E. Beale, K.G. Murphy, M.A. Ghatei, and S.R. Bloom Investigation of structure-activity relationships of oxyntomodulin (Oxm) using Oxm analogs Endocrinology 150 2009 1712 1721
6. X. Du, J.R. Kosinski, J. Lao, X. Shen, A. Petrov, G.G. Chicchi, G.J. Eiermann, and A. Pocai Differential effects of oxyntomodulin and GLP-1 on glucose metabolism Am. J. Physiol. Endocrinol. Metab. 303 2012 E265 E271
7. P.R. Flatt, and C.J. Bailey Abnormal plasma glucose and insulin responses in heterozygous lean (ob/+) mice Diabetologia 20 1981 573 577
8. V.A. Gault, B.D. Kerr, P. Harriott, and P.R. Flatt Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity Clin. Sci. (Lond) 121 2011 107 117
9. N. Irwin, Z.J. Franklin, and F.P. O'Harte desHis(1)Glu(9)-glucagon-[mPEG] and desHis(1)Glu(9)(Lys(30)PAL)-glucagon: long-acting peptide-based PEGylated and acylated glucagon receptor antagonists with potential antidiabetic activity Eur. J. Pharmacol. 709 2013 43 51
10. E. Karra, and R.L. Batterham The role of gut hormones in the regulation of body weight and energy homeostasis Mol. Cell. Endocrinol. 316 2010 120 128
11. 2)Oxm[mPEG-PAL]: A novel chemically modified analogue of oxyntomodulin with antihyperglycaemic, insulinotropic and anorexigenic actions Biochem. Pharmacol. 80 2010 1727 1735
12. J.R. Kosinski, J. Hubert, P. Carrington, G. Chicchi, J. Mu, C. Miller, J. Cao, E. Bianchi, A. Pessi, R. SinhaRoy, D. Marsh, and A. Pocai The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin Obesity 20 2012 1566 1571
13. C.M. Martin, N. Irwin, P.R. Flatt, and V.A. Gault A novel acylated form of (d-Ala(2))GIP with improved antidiabetic potential, lacking effect on body fat stores Biochim. Biophys. Acta 1830 2013 3407 3413
14. N.H. McClenaghan, C.R. Barnett, E. Ah-Sing, Y.H. Abdel-Wahab, F.P. O'Harte, T.W. Yoon, S.K. Swanston-Flatt, and P.R. Flatt Characterization of novel glucose-responsive insulin-secreting cell line, BRIN-BD11, produced by electrofusion Diabetes 45 1996 1132 1140
15. F.P. O'Harte, Z.J. Franklin, E.P. Rafferty, and N. Irwin Characterisation of structurally modified analogues of glucagon as potential glucagon receptor antagonists Mol. Cell. Endocrinol. 381 2013 26 34
16. A. Pocai, P. Carrington, J. Adams, W. Michael, G. Eiermann, L. Zhu, X. Du, A. Petrov, M. Lassman, G. Jiang, F. Liu, C. Miller, L. Tota, G. Zhou, X. Zhang, M. Sountis, A. Santoprete, E. Capito, G. Chicchi, N. Thornberry, E. Bianchi, A. Pessi, D. March, and R. SinhaRoy GLP-1/GCGR dual agonism reverses obesity in mice Diabetes 58 2009 2258 2266
17. A. Pocai Unravelling oxyntomodulin, GLP-1's enigmatic brother J. Endocrinol. 215 2012 335 346
18. A Santroprete, E. Capito, P. Carrington, A. Pocai, M. Finotto, A. Langella, P. Ingallinella, K. Zytko, S. Bufali, S. Cianetti, M. Veneziano, R. SinhaRoy, E. Bianchi, and A. Pessi DPP-IV-resistant, long-acting oxyntomodulin derivatives J. Pept. Sci. 17 2011 270 280
19. C.G. Unson, C.G. Whu, K.J. Fitzpatrick, and R.B. Merrifield Multiple site replacement analogues of glucagon. A molecular basis for antagonist design J. Biol. Chem. 269 1994 12548 12551
20. K. Wynne, A.J. Park, C.J. Small, K. Meeran, M.A. Ghatei, G.S. Frost, and S.R. Bloom Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial Int. J. Obes. 30 2006 1729 1736
21. L. Zhu, C. Tamvakopoulos, D. Xie, J. Dragovic, X. Shen, J.E. Fenyk-Melody, K. Schmidt, A. Bagchi, P.R. Griffin, N.A. Thornberry, and R. SinhaRoy The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: in vivo metabolism of pituitary adenylate cyclise activating polypeptide-(1-38) J. Biol. Chem. 278 2003 22418 22423
22. B.P. Ward, N.L. Ottaway, D. Perez-Tilve, D. Ma, V.M. Gelfanov, M.H. Tschöp, and R.D. Dimarchi Peptide lipidation stabilizes structure to enhance biological function Mol. Metab. 2 2013 468 479