title: Improvement of islet graft function using liraglutide is correlated with its anti-inflammatory properties.
abstract: Liraglutide 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.
  
  
  
  In vitro, rat islets were incubated with 10 μmol·L-1liraglutide for 12 and 24 h. 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 24 h 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 1 month.
  
  
  
  Islet viability and function were preserved and enhanced with liraglutide treatment. Liraglutide decreased CCL2 and IL-6 secretion and macrophage activation after 12 h of culture, while IL-10 secretion was unchanged. However, intracellular levels of ROS were increased with liraglutide treatment at 12 h. 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.
  
  
  
  The 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.
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: A
authors: A
authors: Langlois
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: S
authors: S
authors: Dal
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: K
authors: K
authors: Vivot
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: C
authors: C
authors: Mura
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: E
authors: E
authors: Seyfritz
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: W
authors: W
authors: Bietiger
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: C
authors: C
authors: Dollinger
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: C
authors: C
authors: Peronet
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: E
authors: E
authors: Maillard
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.|Service d'Endocrinologie, Diabète, Maladies Métaboliques, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors: M
authors: M
authors: Pinget
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.|Service d'Endocrinologie, Diabète, Maladies Métaboliques, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors: N
authors: N
authors: Jeandidier
authors: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors: S
authors: S
authors: Sigrist
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D000069450:Liraglutide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017382:Reactive Oxygen Species; D000069450:Liraglutide