title: Liraglutide protects pancreatic β-cells against free fatty acids in vitro and affects glucolipid metabolism in apolipoprotein E-/- mice by activating autophagy.
abstract: The aim of the present study was to determine whether liraglutide (LRG), a long acting glucagon-like peptide 1 analogue, exerted a protective effect on free fatty acid (FFA)‑treated pancreatic β‑cells via activating autophagy. INS‑1 insulinoma pancreatic islet cell lines were treated with FFA and the levels of cell necrosis, apoptosis and autophagy were detected using an MTT assay, flow cytometry and electron microscopy (ECM). A type 2 diabetes mellitus mouse model was established through treatment of mice with a high‑fat diet for 8 weeks and injection of streptozotocin. LRG and autophagy inhibitors were used to investigate the protective effect of LRG on pancreatic β‑cells in vivo. Metabolic indices were measured and pancreatic autophagy was detected. In the INS‑1 cells, viability was higher in the FFA + LRG group compared with the FFA group, while the apoptotic rate was lower (P<0.05). The light chain 3B and p62 autophagy‑associated proteins were upregulated by LRG, while ATG7 and Beclin1 were downregulated. Autophagy inhibitors reduced the protective effect of LRG in the FFA‑treated INS‑1 cells. The type 2 diabetes mouse model was successfully established, termed the HF group, in which LRG was observed to reduce body weight and decrease levels of fasting blood glucose, total cholesterol, serum insulin, triglyceride, low density lipoprotein‑cholesterol and glycosylated hemoglobin (P<0.05), compared with the HF group. However, chloroquine treatment abrogated these effects (P<0.05, compared with the HF + LRG group; P>0.05, compared with the HF group). Autophagosomes were also observed under ECM in the pancreatic tissues of mice in the HF + LRG group. Therefore, LRG induced autophagy and exerted protective effects on pancreatic β-cells in vitro and in vivo.
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, Hangzhou Sanatorium of Nanjing Military Region, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Xingzhen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Laboratory Diagnostics, General Hospital of Jinan Military District, Jinan, Shandong 250031, P.R. China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Laboratory Diagnostics, General Hospital of Jinan Military District, Jinan, Shandong 250031, P.R. China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Laboratory Diagnostics, General Hospital of Jinan Military District, Jinan, Shandong 250031, P.R. China.
authors.forename: Chengjin
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Dajin
authors.initials: D
authors.lastname: Zou
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000633:toxicity*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D051017:Apoptosis Regulatory Proteins; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D005230:Fatty Acids, Nonesterified; D000069450:Liraglutide; D008869:Microtubule-Associated Proteins; D020011:Protective Agents; D044764:Ubiquitin-Activating Enzymes; C561242:Atg7 protein, rat; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat