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

Oxyntomodulin (Oxm) possesses beneficial biological actions for the potential treatment of obesity-diabetes. However, rapid inactivation by dipeptidyl peptidase-4 (DPP-4) results in a short half-life, hindering therapeutic applicability. In the present study, six Oxm analogues namely, (Thr2)Oxm, (As...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	European journal of pharmacology 2014-11, Vol.743, p.69-78
Hauptverfasser:	Lynch, Aisling M., Pathak, Nupur, Flatt, Yasmin E., Gault, Victor A., O’Harte, Finbarr P.M., Irwin, Nigel, Flatt, Peter R.
Format:	Artikel
Sprache:	eng
Schlagworte:	Analogue Animals Appetite - drug effects Blood Glucose - drug effects Cyclic AMP - metabolism Dipeptidyl Peptidase 4 - metabolism Food intake Glucagon - metabolism Glucagon-Like Peptide 1 - metabolism Glucagon-Like Peptide-1 Receptor Glucose - metabolism Glucose homoeostasis Half-Life Hypoglycemic Agents - pharmacology Insulin - metabolism Insulin secretion Male Mice Mice, Inbred C57BL Oxyntomodulin Oxyntomodulin - pharmacology Peptides - pharmacology Receptors, Glucagon - metabolism
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Oxyntomodulin (Oxm) possesses beneficial biological actions for the potential treatment of obesity-diabetes. However, rapid inactivation by dipeptidyl peptidase-4 (DPP-4) results in a short half-life, hindering therapeutic applicability. In the present study, six Oxm analogues namely, (Thr2)Oxm, (Asp3)Oxm, (Aib2)Oxm, (d-Ser2)Oxm, (N-acetyl)Oxm and (d-Ser2)Oxm-Lys-γ-glutamyl-PAL were synthesised and tested for DPP-4 stability and biological activity. Native Oxm, (Thr2)Oxm and (Asp3)Oxm were rapidly degraded by DPP-4, while (Aib2)Oxm, (d-Ser2)Oxm, (N-acetyl)Oxm and (d-Ser2)Oxm-Lys-γ-glutamyl-PAL were resistant to degradation. All peptides stimulated cAMP production (P
ISSN:	0014-2999 1879-0712
DOI:	10.1016/j.ejphar.2014.09.018