title: Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy.
abstract: BACKGROUND
  The pathophysiology of type 2 diabetes is progressive pancreatic beta cell failure with consequential reduced insulin secretion. Glucotoxicity results in the reduction of beta cell mass in type 2 diabetes by inducing apoptosis. Autophagy is essential for the maintenance of normal islet architecture and plays a crucial role in maintaining the intracellular insulin content by accelerating the insulin degradation rate in beta cells. Recently more attention has been paid to the effect of autophagy in type 2 diabetes. The regulatory pathway of autophagy in controlling pancreatic beta cells is still not clear. The aim of our study was to evaluate whether liraglutide can inhibit apoptosis and modulate autophagy in vitro in insulinoma cells (INS-1 cells).
  
  
  METHODS
  INS-1 cells were incubated for 24 hours in the presence or absence of high levels of glucose, liraglutide (a long-acting human glucagon-like peptide-1 analogue), or 3-methyadenine (3-MA). Cell viability was measured using the Cell Counting Kit-8 (CCK8) viability assay. Autophagy of INS-1 cells was tested by monodansylcadaverine (MDC) staining, an autophagy fluorescent compound used for the labeling of autophagic vacuoles, and by Western blotting of microtubule-associated protein I light chain 3 (LC3), a biochemical markers of autophagic initiation.
  
  
  RESULTS
  The viability of INS-1 cells was reduced after treatment with high levels of glucose. The viability of INS-1 cells was reduced and apoptosis was increased when autophagy was inhibited. The viability of INS-1 cells was significantly increased by adding liraglutide to supplement high glucose level medium compared with the cells treated with high glucose levels alone.
  
  
  CONCLUSIONS
  Apoptosis and autophagy were increased in rat INS-1 cells when treated with high level of glucose, and the viability of INS-1 cells was significantly reduced by inhibiting autophagy. Liraglutide protected INS-1 cells from high glucose level-induced apoptosis that is accompanied by a significant increase of autophagy, suggesting that liraglutide plays a role in beta cell apoptosis by targeting autophagy. Thus, autophagy may be a new target for the prevention or treatment of diabetes.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Ze-fang
authors.initials: ZF
authors.lastname: Chen
authors.forename: Yan-bo
authors.initials: YB
authors.lastname: Li
authors.forename: Jun-yong
authors.initials: JY
authors.lastname: Han
authors.forename: Jia-jing
authors.initials: JJ
authors.lastname: Yin
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Li-bo
authors.initials: LB
authors.lastname: Zhu
authors.forename: Guang-ying
authors.initials: GY
authors.lastname: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007340:Insulinoma / Q000473:pathology; D000069450:Liraglutide; D051381:Rats
chemical_list: D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005947:Glucose