Biological activity of GLP-1-analogues with N-terminal modifications

Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo

“…This suggests that increasing the size of the amino acid side chain at Ala 8 , achieved by substituting for either valine or 2-aminobutyric acid, drastically reduces the specificity of DPP IV for GLP-1. This finding is in accordance with previous studies, where Ala 8 of GLP-1 was substituted with glycine (Deacon et al 1998, Burcelin et al 1999, Siegel et al 1999, Doyle et al 2001, serine (Deacon et al 1998, Ritzel et al 1998, Siegel et al 1999, -alanine (Siegel et al 1999), threonine or -aminoisobutyric acid (Deacon et al 1998).…”

“…Taken together with previous data (Siegel et al 1999) (Fehmann et al 1995). Other modifications of the GLP-1 molecule through substitution of Ala 8 have also been reported.…”

International Union of Pharmacology. XXXV. The Glucagon Receptor Family

“…Since the half-life of the naturally occurring peptide in plasma is too short for optimal clinical use, long-acting degradation resistant GLP-1 analogs have now been developed (Deacon et al, 1998;Ritzel et al, 1998;Burcelin et al, 1999a;Siegel et al, 1999;Doyle et al, 2001;Xiao et al, 2001), and these analogs, together with the lizard peptide exendin-4, are being assessed in studies of patients with type 2 diabetes Egan et al, 2002;Juhl et al, 2002).…”

The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells

“…However, the short circulating half-life of the bioactive, intact GLP-1 limits its potential use for the treatment of diabetes (1). Liraglutide, one of the long-acting GLP-1 receptor agonists, resists dipeptidyl peptidase (DPP)-IV degradation by fatty acid (FA) acylation and albumin binding, and has been utilized in clinical practice (2).…”