title: Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways.
abstract: BACKGROUND
  As a new anti-diabetic medicine, Liraglutide (LIRA), one of GLP-1 analogues, has been found to have an anti-atherosclerotic effect. Since vascular smooth muscle cells (VSMCs) play pivotal roles in the occurrence of diabetic atherosclerosis, it is important to investigate the role of LIRA in reducing the harmful effects of high-glucose (HG) treatment in cultured VSMCs, and identifying associated molecular mechanisms.
  
  
  METHODS
  Primary rat VSMCs were exposed to low or high glucose-containing medium with or without LIRA. They were challenged with HG in the presence of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2, or glucagon-like peptide receptor (GLP-1R) inhibitors. Cell proliferation and viability was evaluated using a Cell Counting Kit-8. Cell migration was determined by Transwell migration and scratch wound assays. Flow cytometry and Western blotting were used to determine apoptosis and protein expression, respectively.
  
  
  RESULTS
  Under the HG treatment, VSMCs exhibited increased migration, proliferation, and phosphorylation of protein kinase B (Akt) and ERK1/2, along with reduced apoptosis (all p < 0.01 vs. control). These effects were significantly attenuated with LIRA co-treatment (all p < 0.05 vs. HG alone). Inhibition of PI3K kinase and ERK1/2 similarly attenuated the HG-induced effects (all p < 0.01 vs. HG alone). GLP-1R inhibitors effectively reversed the beneficial effects of LIRA on HG treatment (all p < 0.05).
  
  
  CONCLUSIONS
  HG treatment may induce abnormal phenotypes in VSMCs via PI3K and ERK1/2 signaling pathways activated by GLP-1R, and LIRA may protect cells from HG damage by acting on these same pathways.
authors: Lili
authors: L
authors: Shi
authors: Ye
authors: Y
authors: Ji
authors: Xiaoyan
authors: X
authors: Jiang
authors: Lihong
authors: L
authors: Zhou
authors: Ying
authors: Y
authors: Xu
authors: Yanbo
authors: Y
authors: Li
authors: Wei
authors: W
authors: Jiang
authors: Ping
authors: P
authors: Meng
authors: Xiaomin
authors: X
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000069450:Liraglutide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000097789:Glucagon-Like Peptide-1 Receptor Agonists