The novel GLP-1-gastrin dual agonist, ZP3022, increases ß-cell mass and prevents diabetes in db/db mice.

Diabetes, Obesity & Metabolism

PubMedID: 22862961

Fosgerau K, Jessen L, Lind Tolborg J, Østerlund T, Schæffer Larsen K, Rolsted K, Brorson M, Jelsing J, Skovlund Ryge Neerup T. The novel GLP-1-gastrin dual agonist, ZP3022, increases ß-cell mass and prevents diabetes in db/db mice. Diabetes Obes Metab. 2013;15(1):62-71.
AIM
Diabetes is characterized by ß-cell deficiency, and therefore restoration of ß-cell function has been suggested as a potential therapy. We hypothesized that a novel glucagon-like peptide-1 (GLP-1)-gastrin dual agonist, ZP3022, improves glycaemic control via improvement of ß-cell status in db/db mice.

METHODS
Diabetic mice were studied following short- or long-term treatment with either the GLP-1-gastrin dual agonist or the commercially available GLP-1 agonists (exendin-4 and liraglutide). The effects on glycaemic control were addressed by repeated glucose tolerance tests and/or measurements of HbA1c levels, and pancreatic islet and ß-cell masses were determined by stereology.

RESULTS
ZP3022 and the pure GLP-1 agonists improved glycaemic control after both short- and long-term treatment compared with vehicle. Interestingly, the effect was sustainable only in mice treated with ZP3022. Stereology data displayed a dose-dependent increase of ß-cell mass (p < 0.05) following treatment with ZP3022, whereas no significant effect of liraglutide was observed (ß-cell mass: vehicle 3.7 ± 0.2 mg; liraglutide (30 nmol/kg) 3.4 ± 0.5 mg; ZP3022 (30 nmol/kg) 4.3 ± 0.4 mg and ZP3022 (100 nmol/kg) 5.2 ± 0.4 mg).

CONCLUSION
The novel GLP-1-gastrin dual agonist, ZP3022, improved glycaemic control in db/db mice, and pancreatic islet and ß-cell mass increased significantly following treatment with ZP3022 compared with vehicle.