Abstract：Objective To explore the effects of microRNA-22 (miR-22) on glucose metabolism in patients with gestational diabetes mellitus.Methods The placental tissues of 75 gestational diabetic patients(GDM group) and 75 healthy pregnant people (control group) treated in Guangdong Provincial Corps Hospital of Chinese People's Armed Police Force from January 2018 to January 2019 were collected. A cell model was established by culturing human chorionic villous HTR8/Svneo cells with gradient high glucose, and the expression of cellular miR-22 was analyzed. Synthetic miR-22 mimics or antisense oligonucleotides (suppressors) were transfected into HTR8/Svneo cells. Glucose utilization of cells in vitro was determined by glucose oxidase method. Western blot was used to detect PI3K, AKT, IRS, and Glut4 proteins on the insulin signaling pathway in HTR8/Svneo cells, GDM group and normal control tissues. Plasmids containing wild-type and mutant versions of the target genes were designed and constructed; and the relationship between miR-22 and the target genes was analyzed using a dual luciferase reporter gene system.Results miR-22 expression was significantly lower in GDM placental tissues and cells in the high glucose treatment group than in the control group(P＜0.05), and miR-22 expression was negatively correlated with insulin resistance index. The expression levels of IRS, PI3K, AKT and Glut4 in GDM were significantly lower than those in control group. When miR-22 was expressed, glucose uptake of HTR8/Svneo cells increased and Glut4 expression increased; when miR-22 was inhibited, glucose uptake of HTR8/SVneo cells decreased and GLUT4 expression decreased. When miR-22 was overexpressed or inhibited, the expressions of IRS, PI3K and AKT were significantly decreased. The dual luciferase reporter gene system assay showed that SLC2A4 gene (encoding GLUT4) was the regulatory target of miR-22.Conclusions When insulin tolerance occurs, the expression of miR-22 in placental villi tissues and cells is decreased, and the overexpression of miR-22 can improve the level of sugar uptake in vitro. miR-22 may participate in the pathogenesis of GDM by regulating GLUT4.
李伟, 曾一文, 王婧, 胡可胜, 杨莉. 微小RNA-22对妊娠糖尿病患者糖代谢的影响[J]. 武警医学, 2023, 34(2): 93-96.
LI Wei, ZENG Yiwen, WANG Jing, HU Kesheng, YANG Li. Effects of miR-22 on glucose metabolism in gestational diabetes mellitus. Med. J. Chin. Peop. Armed Poli. Forc., 2023, 34(2): 93-96.
Badakhsh M, Daneshi F, Abavisani M, et al. Prevalence of gestational diabetes mellitus in Eastern Mediterranean region: a systematic review and meta-analysis[J]. Endocrine, 2019,65(3): 505-514.
[2]
Su W J, Chen Y L, Huang P Y, et al. Effects of prepregnancy body mass index, weight gain, and gestational diabetes mellitus on pregnancy outcomes: a population-based study in Xiamen, China, 2011-2018[J]. Ann Nutr Metab, 2019,75(1):31-38.
[3]
Bryant N J, Gould G W. Insulin stimulated GLUT4 translocation-size is not everything[J]. Curr Opin Cell Biol, 2020,65:28-34.
[4]
Bartel D P. MicroRNAs:genomics, biogenesis, mechanism, and function[J].Cell,2004,116:281-97
[5]
Pheiffer C, Dias S, Rheeder P, et al. Decreased expression of circulating miR-20a-5p in South African women with gestational diabetes mellitus[J]. Mol Diagn Ther, 2018, 22(3): 345-352.
Masotti A, Baldassarre A, Fabrizi M, et al. Oral glucose tolerance test unravels circulating miRNAs associated with insulin resistance in obese preschoolers[J].Pediatr Obes, 2017,12(3): 229-238.
[8]
Monika G, Cyril S, Anne-Sophie A, et al. Genetic ablation of mir-22 fosters diet-induced obesity and NAFLD development[J]. J Pers Med , 2020,10(4):e170.
[9]
Shi Z, Zhao C, Guo X, et al. Diabetes differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of eralpha expression in estrogen-induced insulin resistance[J]. Endocrinology, 2014,155(5): 1982-1990.
[10]
Tarazona-Santos E, Fabbri C, Yeager M, et al. Diversity in the glucose transporter-4 gene (SLC2A4) in humans reflects the action of natural selection along the old-world primates evolution[J]. PLoS One, 2010,5:E9827.
[11]
Jan S P, Szukiewicz D P, Zylak M, et al. Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus[J]. J Matem Fetal Neonatal Med, 2019, 32(4):650-659.
Shi Z, Zhao C, Guo X, et al. Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of eralpha expression in estrogen-induced insulin resistance[J]. Endocrinology,2014,155(5):1982-1990.
[14]
Vasudevan S, Tong Y, Steitz J A. Switching from repression to activation: microRNAs can up-regulate translation[J]. Science, 2007, 318(58): 1931-1934.
[15]
Vasudevan S, Steitz J A. AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2[J]. Cell, 2007, 128(6): 1105-1118.
[16]
Huaping L, Jiahui F, Yanru Z,et al. Nuclear miR-320 mediates diabetes-induced cardiac dysfunction by activating transcription of fatty acid metabolic genes to cause lipotoxicity in the heart[J].Cir Res, 2019,125:1106-1120.
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