Improvement of islet graft function using liraglutide is correlated with its anti-inflammatory properties

Background and PurposeLiraglutide improves the metabolic control of diabetic animals after islet transplantation. However, the mechanisms underlying this effect remain unknown. The objective of this study was to evaluate the anti-inflammatory and anti-oxidative properties of liraglutide on rat pancreatic islets in vitro and in vivo. Experimental ApproachIn vitro, rat islets were incubated with 10molL(-1) liraglutide for 12 and 24h. Islet viability functionality was assessed. The anti-inflammatory properties of liraglutide were evaluated by measuring CCL2, IL-6 and IL-10 secretion and macrophage chemotaxis. The anti-oxidative effect of liraglutide was evaluated by measuring intracellular ROS and the total anti-oxidative capacity. In vivo, 1000 islets were cultured for 24h with or without liraglutide and then transplanted into the liver of streptozotocin-induced diabetic Lewis rats with or without injections of liraglutide. Effects of liraglutide on metabolic control were evaluated for 1month. Key ResultsIslet viability and function were preserved and enhanced with liraglutide treatment. Liraglutide decreased CCL2 and IL-6 secretion and macrophage activation after 12h of culture, while IL-10 secretion was unchanged. However, intracellular levels of ROS were increased with liraglutide treatment at 12h. This result was correlated with an increase of anti-oxidative capacity. In vivo, liraglutide decreased macrophage infiltration and reduced fasting blood glucose in transplanted rats. Conclusions and ImplicationsThe beneficial effects of liraglutide on pancreatic islets appear to be linked to its anti-inflammatory and anti-oxidative properties. These findings indicated that analogues of glucagon-like peptide-1 could be used to improve graft survival.