Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China.
School of Nursing, Jilin University, Changchun 130021, China.
Int J Mol Sci. 2023 Feb 21;24(5):4279. doi: 10.3390/ijms24054279.
Compared with diabetic patients with normal blood lipid, diabetic patients with dyslipidemia such as high triglycerides have a higher risk of clinical complications, and the disease is also more serious. For the subjects with hypertriglyceridemia, the lncRNAs affecting type 2 diabetes mellitus (T2DM) and the specific mechanisms remain unclear. Transcriptome sequencing was performed on peripheral blood samples of new-onset T2DM (six subjects) and normal blood control (six subjects) in hypertriglyceridemia patients using gene chip technology, and differentially expressed lncRNA profiles were constructed. Validated by the GEO database and RT-qPCR, lncRNA ENST00000462455.1 was selected. Subsequently, fluorescence in situ hybridization (FISH), real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to observe the effect of ENST00000462455.1 on MIN6. When silencing the ENST00000462455.1 for MIN6 in high glucose and high fat, the relative cell survival rate and insulin secretion decreased, the apoptosis rate increased, and the expression of the transcription factors Ins1, Pdx-1, Glut2, FoxO1, and ETS1 that maintained the function and activity of pancreatic β cells decreased ( < 0.05). In addition, we found that ENST00000462455.1/miR-204-3p/CACNA1C could be the core regulatory axis by using bioinformatics methods. Therefore, ENST00000462455.1 was a potential biomarker for hypertriglyceridemia patients with T2DM.
与血脂正常的糖尿病患者相比,血脂异常(如甘油三酯升高)的糖尿病患者发生临床并发症的风险更高,病情也更严重。对于高甘油三酯血症患者,影响 2 型糖尿病(T2DM)的 lncRNAs 及其具体机制尚不清楚。采用基因芯片技术对高甘油三酯血症患者新诊断的 T2DM(6 例)和正常血对照(6 例)的外周血样本进行转录组测序,构建差异表达的 lncRNA 图谱。通过 GEO 数据库和 RT-qPCR 验证,选择 lncRNA ENST00000462455.1。随后,通过荧光原位杂交(FISH)、实时定量聚合酶链反应(RT-qPCR)、CCK-8 测定、流式细胞术和酶联免疫吸附测定(ELISA)观察 ENST00000462455.1 对 MIN6 的影响。当沉默高糖高脂 MIN6 中的 ENST00000462455.1 时,相对细胞存活率和胰岛素分泌减少,凋亡率增加,维持胰岛β细胞功能和活性的转录因子 Ins1、Pdx-1、Glut2、FoxO1 和 ETS1 的表达降低(<0.05)。此外,我们还发现,通过生物信息学方法,ENST00000462455.1/miR-204-3p/CACNA1C 可能是核心调节轴。因此,ENST00000462455.1 是 T2DM 高甘油三酯血症患者的潜在生物标志物。