title: GLP-1 contributes to increases in PGC-1α expression by downregulating miR-23a to reduce apoptosis.
abstract: GLP-1 can help to overcome problems of liver cells metabolism, not only pancreatic cell. But the explicit mechanism of this effect remains unclear. In recent years, microRNAs have received the attention of researchers and some microRNAs have important implications for diabetes. The mitochondrial protective gene PGC-1α is also closely related to diabetes, and UCP2 is related to anti-mitochondrial oxidative stress, but the mechanism of action of these genes is unclear. In this study, we used HepG2 cell line and used the cell counting kit (CCK) to measure the cell viability with GLP-1(7-36) and/or glucotoxicity. To investigate alterations in gene expression resulting from incubation with GLP-1 (7-36) or hyperglycaemia, the RNA expression levels of miR-23a, PGC-1α, Bak, Bax and UCP2 were quantified using real-time PCR. The protein levels of PGC-1α were determined by western blot. The role of miR-23a in the regulation of PGC-1α was further assessed through cell transfection to downregulate of miR-23a expression. In this study, the viability of HepG2 hepatocytes was decreased under hyperglycaemia, but incubation with 10 nmol/L GLP-1 (7-36) amide for 24 h significantly increased the viability and decreased the mRNA expression levels of Bax and Bak. Incubation with GLP-1(7-36) amide for 24 h attenuated the RNA expression of miR-23a and increased the mRNA and protein expression of PGC-1α. Inhibition of miR-23a expression by cell transfection led to increases in the mRNA and protein expression of PGC-1α. In addition, the mRNA expression of UCP2 increased after incubation with GLP-1(7-36) for 24 h. In conclusion, GLP-1 induced increased expression of mitochondrial protective gene PGC-1α by downregulating miR-23a to inhibit hepatocyte apoptosis and also enhanced UCP2 to reduce apoptosis.
authors: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang 150086, China.
authors: Chi
authors: C
authors: Wang
authors: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang 150086, China. Electronic address: QiangLiedu@hotmail.com.
authors: Qiang
authors: Q
authors: Li
authors: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang 150086, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang 150086, China.
authors: Lin
authors: L
authors: Guo
authors: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang 150086, China.
authors: Chang
authors: C
authors: Guo
authors: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang 150086, China.
authors: Yiqiong
authors: Y
authors: Sun
authors: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Xuefu Road No. 246, Harbin, Heilongjiang 150086, China.
authors: Jinchao
authors: J
authors: Zhang
mesh_terms: D017209:Apoptosis; D002470:Cell Survival; D015536:Down-Regulation; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D052216:Glucagon-Like Peptide 1
keywords: Anti-apoptosis; Glucagon-like peptide-1; MicroRNA-23a; Peroxisome proliferator-activated receptor gamma coactivator 1α; Uncoupling protein 2