Sharjah Institute for Medical Research, University of Sharjah.
Mediclinic Parkview Hospital, Dubai.
Exp Clin Endocrinol Diabetes. 2022 Jan;130(1):22-29. doi: 10.1055/a-1261-5282. Epub 2020 Oct 9.
is a member of the miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of are significantly (<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of reduced insulin content and secretion. Modulation of the expression levels of did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in transfected cells revealed a marked dysregulation of , Pancreatic And Duodenal Homeobox 1 (), and . In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.
miRNA 家族的成员之一,在人类胰岛中表达量最高的 miRNA 之一,与葡萄糖稳态有关。2 型糖尿病(T2DM)患者中 的水平或其在 β 细胞功能中的作用尚不清楚。在本研究中,我们测量了阿联酋 T2DM(有/无并发症)患者和对照组的血清 水平。通过 INS-1(832/13)细胞中转染 let7b-5p 的过表达或沉默来研究其对胰岛素分泌、含量、细胞活力、凋亡和关键功能基因的影响。我们发现,与对照组相比,T2DM 患者或 T2DM 合并并发症患者的血清 水平显著升高(<0.05)。let7b-5p 的过表达增加了胰岛素含量并降低了葡萄糖刺激的胰岛素分泌,而 let7b-5p 的沉默则减少了胰岛素含量和分泌。调节 let7b-5p 的表达水平对细胞活力或凋亡没有影响。对转染细胞中标志性基因的 mRNA 和蛋白表达分析显示, 、Pancreatic And Duodenal Homeobox 1 () 和 明显失调。总之,适当水平的 let7b-5p 对于维持 β 细胞功能至关重要,并且可以作为 T2DM 的生物标志物。