Protective Effects Of GLP-1 On Pancreatic Islets ? Cells Damage Induced By Palmitic Acid And Makes Preliminary Study On Mechanism

Objective: To observe the mouse pancreatic islet ? cell line Min6 induced by glucagon-like peptide-1(GLP-1)analogue liraglutide against palmitic acid(PA)The protective effect of injury and the relationship between the protective effect of liraglutide on Min6 cells and autophagy.Methods: The mouse pancreatic islet ?-cell Min6 was selected as the research object,and palmitic acid was used to establish the pancreatic islet ?-cell injury model.Min6 cells in the logarithmic growth phase were randomly divided into a control group: cultivated with common medium for 24 hours;palmitic acid group: used 0.5 mmol/LPA culture for 24 h;liraglutide + palmitic acid group: first add 100 nmol/L liraglutide for 2 h,then intervene with 0.5 mmol/LPA for 24 h;liraglutide + PA + rapa Rapamycin(RAP)group: pre-cultured with 50 nmol/LRapamycin for 2 h,and then co-cultured with 0.5 mmol/LPA+100 nmol/L liraglutide for 24 h.After the intervention,the growth viability of the cells was detected by CCK8 method;flow cytometry was used to detect the apoptosis of Min6 cells;the reactive oxygen species(ROS)kit was used to detect the level of intracellular ROS;RT-PCR technology was used to determine Min6 cells The expression levels of autophagy-related genes beclin-1mRNA and LC3-?mRNA;DAPI staining was used to observe the effect of palmitic acid on cell morphology.Results: Palmitic acid inhibited the proliferation of Min6 cells in a dose-dependent manner;liraglutide has a two-way regulation effect on the growth of normal Min6 cells,low concentration liraglutide(10-100 nmol/L)promotes cell proliferation,and high concentration liraglutide Lutopeptide(1000 nmol/L)inhibits cell proliferation;liraglutide can antagonize the damage of palmitic acid to Min6 cells,and gradually reduce palmitic acid-mediated damage to Min6 cells in a dose-dependent manner;compared with the control group In the palmitic acid group,the apoptosis rate of Min6 cells increased(P<0.05),the level of intracellular reactive oxygen species also increased significantly(P<0.05),and the expression levels of autophagy-related genes beclin-1 and LC3-? increased(P<0.05),Dense and dense staining of the nucleus,suggesting nuclear condensation;compared with the palmitic acid group,the apoptosis rate of the PA+liraglutide group was reduced(P<0.05),and the level of intracellular reactive oxygen species was reduced(P<0.05),beclin-1,LC3-?mRNA expression level increased(P<0.05);Liraglutide+PA+rapamycin group compared with PA group: intracellular reactive oxygen level decreased,apoptosis rate decreased,beclin-1,LC3-?mRNA expression levels Significantly increased,the liraglutide+PA+rapamycin group compared with the PA+liraglutide group: the intracellular reactive oxygen level was slightly increased(the difference was not statistically significant),the apoptosis rate decreased,beclin-1,LC3-?mRNA expression level increased,rapamycin can enhance the protective effect of liraglutide on Min6 cells.Conclusion:(1)High-fat environment has toxic effects on islet ? cells.(2)GLP-1 analogue liraglutide can promote islet ? cell proliferation,inhibit islet ? cell apoptosis in a high-fat environment,reduce palmitic acid-induced oxidative stress response,antagonize the damage of palmitic acid on Min6 cells,and produce Min6 Cell protection.(3)The protective effect of liraglutide on palmitic acid-induced Min6 cells may be related to enhancing the level of autophagy.