Liraglutide prevents diabetes progression in prediabetic OLETF rats

One of human GLP-1 analogues, liraglutide has been approved as adjuvant therapy to oral medication in T2DM. It was also shown to prevent diabetes in obese subjects and rats. However, it is unknown whether liraglutide can effectively mitigate the effects of prediabetes. We therefore investigate this by treating 12-weeks old Otsuka-Long-Evans-Tokushima fatty (OLETF) rats with liraglutide 50, 100, and 200 μg/kg, respectively twice a day for 12 weeks. Eight Long-Evans-Tokushima-Otsuka (LETO) rats with saline injection served as normal controls. Body weight, food intake, lipid profiles, inflammatory markers (fibrinogen, Hs-CRP, IL-6, TNFα, and PAI-1), glycemic metabolism and insulin sensitivity, and apoptotic factors (Bcl-2 and Bax) expression were monitored. We found that 12-week old OLETF rats had significantly increased body weight, food intake, serum levels of lipid profiles, inflammatory markers, and insulin compared to LETO rats. FPG level was significantly increased but still lower than 7mmol/L without impaired glucose tolerance (IGT). After 12 weeks, vehicle-treated OLETF rats had further deterioration in IFG, IGT, insulin resistance, lipid profiles, and inflammatory state. Pancreatic islets were hypertrophic with distorted structure, scarring, and inflammatory cell infiltration. However, in the three liraglutide-treated groups, IFG, IGT, the increased lipid profiles and inflammatory markers were reversed. Insulin resistance was similar to the level before the treatment. Moreover, liraglutide restored the islet structure, up-regulated Bcl-2 expression and down-regulated Bax expression. It indicated that liraglutide could suppress diabetes onset in OLETF rats with prediabetes, probably by reserving β cell function via regulating apoptotic factors as well as ameliorating lipid metabolism and inflammatory reactions.