title: Glucagon-like peptide-1 effects lipotoxic oxidative stress by regulating the expression of microRNAs.
abstract: Aim to confirm whether the treatment of GLP-1 can modulated body weight, lipid metabolism, insulin content, pancreas oxidative stress, improved T-AOC, MDA levels related to FFA-Induced oxidative stress in C57BL/6 mice and INS-1 cells. In this study, GLP-1 makes the expression of AMPK, PPARα, CPT1A and SIRT1 increased, and the expression of SREBP1c, miR-33 and miR-370 decreased. Interestingly, the effects of GLP-1 were less dose dependent as GLP-1 regulated the FFA, which related to gene expression at much lower doses (3 μg/kg, 10 mM, mice and INS-1 respectively) and effects were relatively maintained at higher dose (30 μg/kg, 100 mM, mice and INS-1 respectively) as well. Subsequently, the analysis showed that inhibited expression of miR-33 and miR-370 upregulated the expression of CPT1A and SIRT1, reversely mimics. These results demonstrated for the first time that GLP-1 improve lipotoxic oxidative stress of pancreas by regulate expression of microRNAs.
authors.affiliation: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang, 150086, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang, 150086, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang, 150086, China. Electronic address: qianglihmu@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002460:Cell Line; D003920:Diabetes Mellitus / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics; D018384:Oxidative Stress; D010179:Pancreas; D051381:Rats; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; C580642:MIRN33 microRNA, rat; C551449:MIRN370 microRNA, mouse; C000600513:MIRN370 microRNA, rat; D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse; D009841:Oligonucleotides; D052216:Glucagon-Like Peptide 1; C558401:CPT1B protein, mouse; D002334:Carnitine O-Palmitoyltransferase; C583748:carnitine palmitoyltransferase-1a, rat; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: Glucagon-like peptide-1; Lipotoxic oxidative stress; microRNA-33; microRNA-370