title: Glucagon-like peptide-1 analog-mediated protection against cholesterol-induced apoptosis via mammalian target of rapamycin activation in pancreatic βTC-6 cells -1mTORβTC-6.
abstract: BACKGROUND
  Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic β-cells against glucolipotoxicity via activation of the Akt pathway. The present study investigated the protective effects of the GLP-1 analog liraglutide against cholesterol-induced lipotoxicity and the mechanisms involved.
  
  
  METHODS
  The mouse βTC-6 pancreatic β-cell line was preincubated for 30 min with 10 nmol/L liraglutide alone or in combination with the mammalian target of rapamycin (mTOR) inhibitor rapamycin (1 μmol/L) before being exposed to 5 mmol/L cholesterol for 6 h. 4',6'-Diamidino-2-phenylindole (DAPI) staining and Western blot analyses were used to assess the effects of liraglutide on cholesterol-induced apoptosis and the phosphorylation of Akt and mTOR.
  
  
  RESULTS
  Cholesterol significantly promoted cell apoptosis and attenuated the phosphorylation of Akt and mTOR, effects that were significantly reversed by liraglutide. Furthermore, rapamycin pretreatment alone significantly increased cholesterol-induced apoptosis compared with cholesterol-treated cells without any other pretreatment.
  
  
  CONCLUSIONS
  The data indicate that mTOR signaling is an essential mediator in the protection of pancreatic β-cells against cholesterol-induced apoptosis by a GLP-1 analog.
authors.affiliation: Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Zhou
authors.forename: Jiahua
authors.initials: J
authors.lastname: Wu
authors.forename: Fenping
authors.initials: F
authors.lastname: Zheng
authors.forename: Mengshi
authors.initials: M
authors.lastname: Jin
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002784:Cholesterol / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007340:Insulinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069450:Liraglutide; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D002784:Cholesterol; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: apoptosis; cholesterol; glucagon-like peptide-1; mammalian target of rapamycin; β-cells; 关键词：凋亡，β-细胞，胆固醇，胰高血糖素样多肽-1，mTOR