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

Aim Diabetes is characterized by beta-cell deficiency, and therefore restoration of beta-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 beta-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 beta-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 beta-cell mass (p < 0.05) following treatment with ZP3022, whereas no significant effect of liraglutide was observed (beta-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 beta-cell mass increased significantly following treatment with ZP3022 compared with vehicle.