Roy Dipayan, Purohit Purvi, Khokhar Manoj, Modi Anupama, Shukla Ravindra Kumar Gayaprasad, Chaudhary Ramkaran, Sankanagoudar Shrimanjunath, Sharma Praveen
Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, India.
Indian Institute of Technology (ITT)-Madras, Chennai, India.
J Obes Metab Syndr. 2023 Mar 30;32(1):64-76. doi: 10.7570/jomes22010. Epub 2023 Mar 15.
Growth differentiation factor-15 (GDF-15) is involved in insulin resistance and diabetes. In this study, we determine the associations of GDF-15 with miR-181b-5p, miR-330-3p, mothers against decapentaplegic homolog 7 (SMAD7), and insulin resistance in visceral adipose tissue (VAT) and peripheral blood mononuclear cells (PBMCs) in type 2 diabetes mellitus (T2DM) patients.
Sixty patients, equally divided into those with T2DM and non-diabetic controls, were recruited for gene expression analysis. Protein-protein interaction (STRING), target prediction (miRNet), and functional enrichment were conducted accordingly.
Our study showed that VAT and PBMCs had similar expression profiles, where GDF-15 and miR-181b-5p were upregulated, whereas SMAD7 and miR-330-3p were downregulated. Serum GDF-15 could differentiate between T2DM and non-diabetic patients (<0.001). Target prediction revealed a microRNA (miRNA)-messenger RNA regulatory network, transcription factors, and functional enrichment for the miRNA that suggested involvement in T2DM pathogenesis.
VAT GDF-15 is associated with insulin resistance and is possibly regulated by miR-181b-5p, miR-330-3p, and SMAD7 in T2DM.
生长分化因子-15(GDF-15)与胰岛素抵抗和糖尿病有关。在本研究中,我们确定了2型糖尿病(T2DM)患者内脏脂肪组织(VAT)和外周血单个核细胞(PBMC)中GDF-15与miR-181b-5p、miR-330-3p、母亲对十二指节蛋白同源物7(SMAD7)以及胰岛素抵抗之间的关联。
招募60名患者,平均分为T2DM患者组和非糖尿病对照组,进行基因表达分析。相应地进行了蛋白质-蛋白质相互作用(STRING)、靶标预测(miRNet)和功能富集分析。
我们的研究表明,VAT和PBMC具有相似的表达谱,其中GDF-15和miR-181b-5p上调,而SMAD7和miR-330-3p下调。血清GDF-15可区分T2DM患者和非糖尿病患者(<0.001)。靶标预测揭示了一个微小RNA(miRNA)-信使RNA调控网络、转录因子以及该miRNA的功能富集,提示其参与T2DM发病机制。
在T2DM中,VAT中的GDF-15与胰岛素抵抗相关,可能受miR-181b-5p、miR-330-3p和SMAD7调控。