title: The Neuroprotection of Liraglutide Against Ischaemia-induced Apoptosis through the Activation of the PI3K/AKT and MAPK Pathways.
abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases glucose-dependent insulin secretion to reduce the glucose level. Liraglutide, a long-acting GLP-1 analogue, has been found to have neuroprotective action in various experimental models. However, the protective mechanisms of liraglutide in ischaemic stroke remain unclear. Here, we demonstrated that liraglutide significantly decreased the infarct volume, improved neurologic deficits, and lowered stress-related hyperglycaemia without causing hypoglycaemia in a rat model of middle cerebral artery occlusion (MCAO). Liraglutide inhibited cell apoptosis by reducing excessive reactive oxygen species (ROS) and improving the function of mitochondria in neurons under oxygen glucose deprivation (OGD) in vitro and MCAO in vivo. Liraglutide up-regulated the phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinases (ERK) and inhibited the phosphorylation of c-jun-NH2-terminal kinase (JNK) and p38. Moreover, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and/or the ERK inhibitor U0126 counteracted the protective effect of liraglutide. Taken together, these results suggest that liraglutide exerts neuroprotective action against ischaemia-induced apoptosis through the reduction of ROS and the activation of the PI3K/AKT and mitogen-activated protein kinase (MAPK) pathways. Therefore, liraglutide has therapeutic potential for patients with ischaemic stroke, especially those with Type 2 diabetes mellitus or stress hyperglycaemia.
authors.affiliation: Stroke Center and Department of Neurology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Stroke Center and Department of Neurology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guangdong Hongkong and Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, China.
authors.forename: Zhongshan
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Stroke Center and Department of Neurology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.affiliation: Guangdong Hongkong and Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Stroke Center and Department of Neurology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Guangdong Hongkong and Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, China.|Department of Human Anatomy, Jinan University School of Medicine, Guangzhou, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Stroke Center and Department of Neurology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D000069450:Liraglutide / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D020521:Stroke / Q000150:complications / Q000188:drug therapy
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000069450:Liraglutide; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt