A novel DPP IV-resistant C-terminally extended glucagon analogue exhibits weight-lowering and diabetes-protective effects in high-fat-fed mice mediated through glucagon and GLP-1 receptor activation.

Diabetologia

PubMedID: 24962667

Lynch AM, Pathak N, Pathak V, O'harte FP, Flatt PR, Irwin N, Gault VA. A novel DPP IV-resistant C-terminally extended glucagon analogue exhibits weight-lowering and diabetes-protective effects in high-fat-fed mice mediated through glucagon and GLP-1 receptor activation. Diabetologia. 2014;.
AIMS/HYPOTHESIS
Modification of the structure of glucagon could provide useful compounds for the potential treatment of obesity-related diabetes.

METHODS
This study evaluated N-acetyl-glucagon, (D-Ser(2))glucagon and an analogue of (D-Ser(2))glucagon with the addition of nine amino acids from the C-terminal of exendin(1-39), namely (D-Ser(2))glucagon-exe.

RESULTS
All analogues were resistant to dipeptidyl peptidase IV degradation. N-Acetyl-glucagon lacked acute insulinotropic effects in BRIN BD11 cells, whereas (D-Ser(2))glucagon and (D-Ser(2))glucagon-exe evoked significant (p?
CONCLUSIONS/INTERPRETATION
This study emphasises the potential of (D-Ser(2))glucagon-exe for the treatment of obesity-related diabetes.