Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt.
Clinical Pathology, Medical Ain Shams Research Institute, Ain Shams University, Cairo, Egypt.
Front Endocrinol (Lausanne). 2023 May 8;14:1131171. doi: 10.3389/fendo.2023.1131171. eCollection 2023.
Type 2 diabetes mellitus (T2DM) is a major global health concern. It usually develops gradually and is frequently preceded by undetectable pre-diabetes mellitus (pre-DM) stage. The purpose of this study was to identify a novel set of seven candidate genes associated with the pathogenesis of insulin resistance (IR) and pre-DM, followed by their experimental validation in patients' serum samples.
We used the bioinformatics tools and through a two-step process, we first identified and verified two mRNA candidate genes linked to insulin resistance molecular pathogenesis. Second, we identified a non-coding RNAs related to the selected mRNAs and implicated in the insulin resistance molecular pathways followed by pilot study for the RNA panel differential expression in 66 patients with T2DM, 49 individuals with prediabetes and 45 matched controls using real time PCR.
The levels of expression of TMEM173 and CHUK mRNAs, hsa-miR (-611, -5192, and -1976) miRNAs gradually increased from the healthy control group to the prediabetic group, reaching their maximum levels in the T2DM group (p <10-3), whereas the levels of expression of RP4-605O3.4 and AC074117.2 lncRNAs declined gradually from the healthy control group to the prediabetic group, reaching their lowest levels in the T2DM group (p <10-3). TMEM173, CHUK mRNAs, hsa_miR (-611 & -1976) and RP4-605O3.4 lncRNA were useful in distinguishing insulin resistant from insulin sensitive groups. miR_611 together with RP4-605O3.4 exhibited significant difference in good versus poor glycemic control groups.
The presented study provides an insight about this RNA based STING/NOD/IR associated panel that could be used for PreDM-T2DM diagnosis and also as a therapeutic target based on the differences of its expression level in the pre-DM and T2DM stages.
2 型糖尿病（T2DM）是一个主要的全球健康问题。它通常是逐渐发展的，并且经常在未被察觉的糖尿病前期（pre-DM）阶段之前发生。本研究的目的是确定一组与胰岛素抵抗（IR）和 pre-DM 发病机制相关的七个候选基因，然后在患者的血清样本中对其进行实验验证。
我们使用生物信息学工具，并通过两步法，首先鉴定和验证与胰岛素抵抗分子发病机制相关的两个 mRNA 候选基因。其次，我们鉴定了与选定的 mRNAs 相关的非编码 RNA，并涉及胰岛素抵抗分子途径，然后对 66 例 T2DM 患者、49 例 pre-DM 个体和 45 名匹配对照者的 RNA 谱差异表达进行了先导研究，使用实时 PCR。
TMEM173 和 CHUK mRNA 的表达水平从健康对照组到 pre-DM 组逐渐升高，在 T2DM 组达到最高水平（p<10-3），而 RP4-605O3.4 和 AC074117.2 lncRNA 的表达水平则从健康对照组到 pre-DM 组逐渐降低，在 T2DM 组达到最低水平（p<10-3）。TMEM173、CHUK mRNA、hsa_miR（-611 & -1976）和 RP4-605O3.4 lncRNA 可用于区分胰岛素抵抗和胰岛素敏感组。miR_611 与 RP4-605O3.4 一起在良好和不良血糖控制组之间存在显著差异。
本研究提供了一个关于基于 RNA 的 STING/NOD/IR 相关面板的见解，该面板可用于 pre-DM-T2DM 诊断，并且还可以作为一个治疗靶点，基于其在 pre-DM 和 T2DM 阶段的表达水平的差异。
