Diabetologie und Stoffwechsel 2014; 9 - P104
DOI: 10.1055/s-0034-1374961

Effects of liraglutide in an adolescent prediabetic transgenic pig model

E Streckel 1, C Braun-Reichhart 1, N Herbach 2, M Ritzmann 3, R Wanke 2, E Wolf 1, S Renner 1
  • 1Chair for Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-University, Oberschleißheim, Germany
  • 2Institute of Veterinary Pathology, Faculty of Veterinary Medicine, Ludwig-Maximilians-University, Munich, Germany
  • 3Clinic for Swine, Ludwig-Maximilians-University, Oberschleißheim, Germany

Aim: To evaluate the effect of the glucagon-like peptide-1 analogue liraglutide on glycemic control, body weight, food intake, alpha- and beta-cell mass in adolescent transgenic pigs expressing a dominant-negative glucose-dependent insulinotropic polypeptide receptor (GIPRdn) (Renner et al., Diabetes 59:1228 – 1238, 2010).

Methods: GIPRdn transgenic pigs were treated with 0.6 mg – 1.8 mg liraglutide or placebo subcutaneously once daily for 90 days. Glucose tolerance was evaluated in a mixed meal oral test. Finally animals were subjected to necropsy and alpha- as well as beta-cell mass were determined by quantitative-stereological analysis.

Results: Liraglutide treatment led to marked and sustained reductions in body weight gain (30 – 40%) and food intake (20 – 50%) compared to placebo treatment. In the mixed meal test performed after the treatment period, liraglutide-treated animals exhibited only a moderate increase of blood glucose, probably due to the known effect of liraglutide on gastric emptying. Additionally, AUC insulin was significantly smaller in liraglutide- vs. placebo-treated animals. Further, liraglutide treatment reduced HOMA-IR and increased several insulin sensitivity indices. Alpha- and beta-cell mass related to body weight did not differ between liraglutide- and placebo-treated animals.

Conclusion: The GIPRdn transgenic pig model recapitulates principle clinical effects of liraglutide observed in type 2 diabetic humans. However, the reduction of body weight gain observed in adolescent pigs was much more dramatic than the weight reduction seen in adult patients; thus special care is warranted in treatment trials involving adolescent patients. There was no evidence for an increasing effect of liraglutide on alpha- and beta-cell mass.